MECHANISTIC INVESTIGATIONS INTO THE THERMAL C-C BOND FORMING CYCLIZATION OF METAL PYRIDINE-ENAMIDE COMPLEXES AND THE SYNTHESIS AND REACTIVITY OF CATIONIC AND NEUTRAL IRON(IV) ALKYLIDENE COMPLEXES A Dissertation Presented to the Faculty of the Graduate School of Cornell University In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy by Brian Lindley February 2016 © 2016 Brian Lindley MECHANISTIC INVESTIGATIONS INTO THE THERMAL C-C BOND FORMING CYCLIZATION OF METAL PYRIDINE-ENAMIDE COMPLEXES AND THE SYNTHESIS AND REACTIVITY OF CATIONIC AND NEUTRAL IRON(IV) ALKYLIDENE COMPLEXES Brian Lindley, Ph. D. Cornell University 2016 A series of first row transition metal pyridine-enamide complexes has been synthesized. In the course of reactivity studies, it was discovered that heating a solution of the cobalt bis(pyridine-enamide) pyridine adduct resulted in intraligand CC coupling to form an indolamide ligand. Control experiments with the corresponding lithium pyridine-enamide afforded the same indolamide. In order to probe the mechanism of cyclization, deuterium labeling experiments for the lithium pyridineenamide compound were conducted. Careful kinetics measurements supported a mechanism consisting of reversible hydrogen transfer followed by rate-determining CC bond formation, in accord with computational results. Iron(II) complexes bearing cyclometalated benzyldialkylphosphine ligands were synthesized via a salt metathesis approach by treating FeCl2(PMe3)2 with two equivalents of (2-lithiobenzyl)diphenyl- and (2-lithiobenzyl)dicyclohexylphosphine reagents. For the phenyl derivative, a 6-coordinate diamagnetic complex containing two chelating phosphine ligands and two trimethylphosphine ligands was obtained. Contrarily, for the cyclohexyl derivative, a 5-coordinate complex containing two chelating phosphines and one molecule of trimethylphosphine was obtained. This compound is paramagnetic with an S = 1 ground state. Efforts to synthesize Fe(IV) alkylidenes by treating these Fe(II) complexes with diphenyldiazomethane were ultimately unsuccessful. An iron(II) vinyl complex was synthesized by reaction of cis-Me2Fe(PMe3)4 with a 2-propynylaniline benzylidene ligand. Protonation of this complex with [H(OEt2)2]BArF4 (BArF4 = B(3,5-(CF3)2C6H3)4) gave access to a cationic Fe(IV) alkylidene complex. By treating this complex with different anionic nucleophiles, a rare series of neutral Fe(IV) alkylidene complexes was obtained. In addition, treatment of the cationic alkylidene complex with MeMgCl afforded a novel Fe(IV) methyl complex. Attempts at catalyzing olefin metathesis with both the cationic and neutral alkylidene complexes proved unsuccessful, likely due to recalcitrant phosphine dissociation and the sterics at the alkylidene carbon. BIOGRAPHICAL SKETCH Brian was born on March 5, 1988 in Binghamton, NY. Raised by John and Susan Lindley in Vestal NY, Brian was the sixth of eight children and learned a great deal from his siblings Megan, Patrick, David, Kevin, Jennifer, Sean, and Eric. Despite his middle school desires to become a math teacher, his interests quickly shifted towards chemistry while attending Seton Catholic Central High School. After graduating from high school in 2006, he attended the University of Rochester, where he majored in chemistry and minored in chemical engineering. During the summer of 2008, Brian joined Rich Eisenberg’s group at Rochester to study light-driven cobalt-catalyzed hydrogen production under the training of Dr. Theodore Lazarides. This experience was instrumental in shaping Brian’s interest in inorganic chemistry. After working for Rich on a senior research project involving similar chemistry, Brian graduated in 2010 and moved to Ithaca, NY to pursue his PhD in Chemistry at Cornell University. Brian gravitated toward Pete Wolczanski’s group at Cornell and was quickly welcomed into the group. After a brief foray into tri(tert-butyl)silylthiolate chemistry, Brian shortly set his sights on developing an iron olefin metathesis catalyst, with intermittent investigations into pyridine-enamide chemistry, Pd-catalyzed trifluoromethylation, and water oxidation. Brian intends on pursuing his long-held goal of becoming a university chemistry professor. iii Dedicated to Mom and Dad iv ACKNOWLEDGMENTS I would first like to acknowledge my advisor, Pete Wolczanski, for providing me with seemingly endless ideas for new reaction frontiers. I am forever grateful for his understanding, his patience, his pep talks, and his support. His enthusiasm for and extensive knowledge of organometallic chemistry was instrumental in my enhanced interest in the subject and will undoubtedly serve me well in my future endeavors. I would also like to thank several other Cornell Chemistry faculty members. I would like to thank Geoff Coates and Will Dichtel for serving on my committee. I would also like to thank Dave Collum for his help with several of my lithium questions and Chad Lewis for his help with ligand synthesis. A special thanks goes to Kyle Lancaster, who gave me the opportunity to be his teaching assistant for Chem 4100 for three semesters. I consider these experiences to be some of the most important in my growth as a teacher, and I will forever be indebted to him for the wealth of knowledge I acquired under his tutelage. I would like to thank the several collaborators who have been instrumental in my several research projects. I specifically extend my thanks to Karsten Meyer, Jörg Sutter, and Mario Adelhardt at FAU Erlangen-Nuremburg for their collection of Mössbauer data, Thomas Cundari for his computational assistance, and Emil Lobkovsky for solving all of my X-ray crystal structures. I would also like to thank Anne LaPointe for offering her time and assistance in setting up high throughput experiments for the attempted palladium-catalyzed trifluoromethylation of arylboronic acids. I am also thankful to Larry Stull and Dave Neish from Building Services for their generous help in fixing countless problems throughout the lab. I would next like to thank all of the other Wolczanski group members that have helped me and have been great friends during my time at Cornell. Though our time in the group together was brief, I would first like to thank Elliott Hulley for generously v giving of his time to answer any questions that I had, and for inspiring me to try to do the same. I would also like to thank Erika Bartholomew for teaching me how to make FeMe2(PMe3)4 and for always helping me when I was struggling. Next, I would like to thank Wes Morris for talking sports and especially for talking science. He was always my go-to guy if I needed to vet some new ligand idea. I am also thankful to Valerie Williams, who helped me grow as a scientist and served in a difficult role as my Wednesday post-beers walking buddy. Among the newer crowd, I would like to thank Brian Jacobs for breaking up my day with interesting conversation topics, whether scientific or not. I also thank Spencer Heins, the newest addition to the group, for his enthusiasm about chemistry and for serving an integral role at The Nines after the graduation of the previous group members. I would also like to thank Ala’aeddeen Swidan for reinvigorating my interest in Fe(IV) alkylidene complexes and for always bringing a calming presence to the lab. Lastly, I would like to thank Rishi Agarwal for helping me out with various projects and for putting up with my unpredictable moods, especially during thesis writing. Among my early Rochester influences, I would like to first and foremost thank Rich Eisenberg for getting me interested in inorganic chemistry and serving as a model advisor and friend. I would also like to thank Ted Lazarides, my first research mentor, for being patient with my mistakes and for the conversations we had over late night pizza after long days of running columns. I am also grateful for Theresa McCormick, another research mentor, for always being generous with her time and assistance. I would like to especially thank Thomas Krugh for giving me my first teaching assistant position and for always looking out for my best education and career interests. Last, but not least, I would like to thank my family and friends for their vi support, especially during the tougher times of graduate school. I will always cherish the comforting, and often humorous, words of my mom and dad during our telephone conversations, as well as the words of support and motivation from my siblings. I also would like to thank my fellow classmates, especially Dan, Craig, Greg, Jay, Kait, Katie, and Michael, who maintained my sanity and provided me with several unforgettable memories. I also thank all the other chemistry people I have interacted with over the past 5 years. They have truly made it a joy and a pleasure to be at Cornell. vii TABLE OF CONTENTS Biographical Sketch……………………………………………………………………iii Dedication ……………………………………………………………………………..iv Acknowledgements …………………………………………………………………….v List of Figures…………………………………………………………………………..x List of Schemes ……………………………………………………………………….xii List of Tables………………………………………………………………………….xiv 1. Synthesis and Benzylic C-H Activation of 1st Row Transition Metal and Lithium Pyridine-enamide Complexes. Introduction …………………………………………………………….1 Results and Discussion …………………………………………………4 Conclusions……………………………………………………………33 Experimental…………………………………………………………..34 References …………………………………………………………….50 2. Iron(II) Complexes Bearing Ortho-metalated Benzyldialkylphosphine Ligands as Potential Precursors to Iron(IV) Alkylidene Complexes. Introduction ..…………………………………………………………54 Results and Discussion………………………………………………..57 Conclusions ...…………………………………………………………65 Experimental ………………………………………………………….66 References …………………………………………………………….71 3. Protonation of Fe(II) Vinyl Complexes as a Convenient Entry into Cationic and Neutral Fe(IV) Alkylidene Complexes. Introduction……………………………………………………………73 Results and Discussion ………………………………………………..73 Conclusions....…………………………………………………………93 Experimental…………………………………………………………..94 References……………………………………………………………104 Appendix 1: Vinyl and Imine C-H Activation Attempts with cis-Me2Fe(PMe3)4. Introduction…………………………………………………………..106 viii Results and Discussion ………………………………………………106 Experimental…………………………………………………………116 References……………………………………………………………124 Appendix 2: Synthesis and Attempted Water Oxidation Reactivity of Dihydroxyand Tetrahydroxysalen Ligands and the Corresponding Manganese(III) Complexes. Introduction ………………………………………………………….125 Results and Discussion ………………………………………………126 Experimental…………………………………………………………130 References……………………………………………………………132 ix LIST OF FIGURES Figure 1.1 Figure 1.2 Figure 1.3 Figure 1.4 Figure 1.5 Figure 1.6 Figure 1.7 Figure 1.8 Figure 1.9 Previous examples from the group involving pyridine-imine-containing ligands.………………………………………………………………….2 Molecular structure of (pyEA-AriPr2)2Fe (1-Fe).………………………7 Molecular structure of (pyEA-AriPr2)2Copy (1-Co-py). ……………….8 Molecular structure of (κ-C,N-pyEA-AriPr2)3Co (2).…………………10 UV-Vis spectrum of 2 in THF.………………………………………...12 Molecular structure of {κ-N,N-N(C6H3(2-iPr)CMe2C(Me)(2-py))}2Co (3-Co).…………………………………………………………………17 Reaction progress of (pyEA-ArEt2)Li cyclization monitored by 1H NMR. ………………………………………………………………….18 Eyring plot for the conversion of (pyEA-ArMe2)Li to {κ-N,NN(C6H3(2-Me)CH2C(Me)(2-py))}Li. …………………………………20 Calculations of (pyEA-ArMe2)Li rearrangement conducted at MP2 and M06 levels of theory at 403.15 K.…………………………………….22 Figure 1.10 Figure 1.11 Intramolecular equilibrium benzyl-vinyl H/D exchange for (pyEAC6H4-o-CD3)Li.………………………………………………………..24 EIE Computations for the thermolysis of (pyEA-C6H4-o-CD3)L……..26 Figure 1.12 Computational EIE analysis for the pre-equilibrium hydrogen transfer. ………………………………………………………………..27 Figure 1.13 Synthesis of indolines via hydrogenation of indoles and hydrogenation of 3H-indoles. …………………………………………………………31 Figure 1.14 Indoline synthesis via Pd-catalyzed aryl C-H amination and Cucatalyzed coupling. ………………………………………………........32 Figure 2.1 Select examples of olefin metathesis catalysts.……………………….54 Figure 2.2 Possible isomers for compound 4. Note: enantiomers of C, D, and E have been excluded for simplicity.……………………………………61 x Figure 2.3 Figure 3.1 Figure 3.2 D-orbital splitting diagram of compound 5 in idealized tbp geometry. ……………………………………………………………...62 X-Ray Crystal Structure of 9.…………………………………………80 Important orbital interaction resulting in favorable N2 binding for 10Me-N2.…………………………………………………………………83 xi LIST OF SCHEMES Scheme 1.1 Synthesis of Li and K pyridine enamides and the parent pyridine imines.…………………………………………………………………..4 Scheme 1.2 Synthesis of 1-M (M = Cr, Mn, Fe, Co-py) and 2.……………………..5 Scheme 1.3 Scheme 1.4 Calculated thermodynamic parameters for the reaction of 1-M with H2. ……………………………………………………………………..13 Reactions of 1-Fe with H2, nBu3SnH, dihydroanthracene, and tBuI.….14 Scheme 1.5 Thermolyses and aqueous quench of 1-M (M = Cr, Mn, Fe, Co-py)....15 Scheme 1.6 Proposed pathway for conversion of 1-Co-py to 3-Co.……………….21 Scheme 1.7 EIE analysis for the thermolysis of (pyEA-C6H4-o-CD3)Li.………….25 Scheme 1.8 Parallel experiments to determine KIE of cyclization reaction.………28 Scheme 1.9 Previous literature examples of metal-templated indolamide formation.……………………………………………………………...29 Scheme 1.10 Possible hydrogen transfer pathways and interconversion of resonance structures.……………………………………………………………...30 Scheme 2.1 Representative examples of the synthesis of iron alkylidene complexes. …………………………………………………………….55 Scheme 2.2 Original proposal for iron alkylidene formation.……………………...57 Scheme 2.3 Reaction of FeBr2(THF)2 with LiBnCy2P·OEt2 in the presence of various ligands.………………………………………………………..64 Scheme 3.1 Proposed protonation strategy for the synthesis of Fe(IV) alkylidenes. ……………………………………………………………73 Scheme 3.2 Reactivity of 9 with select alkenes. …………………………………...81 Scheme 3.3 Competing Reaction Pathways of 9 with anionic nucleophiles. ……...82 Scheme 3.4 Reaction pathway for the formation of 10-Bn-N2. ……………………85 xii Scheme 3.5 Proposed mechanism for reaction of 9 with MesLi.…………………..89 Scheme 3.6 Possible degradation pathways for 12. ………………………………..90 Scheme 3.7 Proposed synthesis of Fe(IV) complex with less hindered alkylidene..92 Scheme 3.8 Proposed synthesis of a 14-electron Fe alkylidene complex.…………92 Scheme A1.1 Examples of successfully metalated tridentate ligands.……………...108 Scheme A1.2 Synthesis of 1,1-dimethylallylamine.………………………………...109 Scheme A1.3 Synthesis of pyphp.…………………………………………………..111 Scheme A1.4 Proposed mechanism for the formation of A1-H.…………………....115 Scheme A2.1 Proposal for water oxidation with dihydroxysalen (DHsalen) complexes.……………………………………………………………126 xiii LIST OF TABLES Table 1.1 Table 1.2 Table 3.1 Table 3.2 Select Crystallographic and Refinement Data for 1-Fe, 1-Co-py, 2, and 3-Co. ……………………………………………………………….9 Kinetics of (pyEA-ArRR')Li (ArRR' = 2,6-R2-C6H3 (R = iPr, Et, Me), 2-Me-C6H4) and (pyEA-AriPr2)2M (1-M, M = Cr, Mn, Fe, Co-py) rearrangement to corresponding indolamides.………………………...19 Alkylidene Fe=C bond lengths and 13C NMR shifts of select Fe=C complexes. …………………………………………………………….79 Select Crystallographic and Refinement Data for 9. ………………….80 xiv Chapter 1 Synthesis and Benzylic C-H Activation of 1st Row Transition Metal and Lithium Pyridine-enamide Complexes Introduction Redox non-innocent (RNI) ligands, i.e. ligands that can accommodate more than one redox state, have been widely studied in both synthetic and biological systems.1–5 RNI ligands have orbitals of similar energy to transition metal d-orbitals, thus giving rise to highly covalent, delocalized metal complexes which can undergo formally ligand-centered and/or metal-centered redox reactions. Several representative examples of well-studied RNI ligand frameworks include dithiolenes,6 o-quinones,7,8 α-diimines,9,10 pyridine diimines (PDI),11–32 αiminopyridines,33–38 and amidophenolates.39,40 For some metal complexes, the RNI ligand alone serves as the electron reservoir, permitting 2-electron processes in the absence of metal oxidation state changes. This is especially desirable for early transition metals, which are less amenable to redox processes. For example, Heyduk has reported oxidative addition, reductive elimination, and group transfer for d0 metal complexes, all of which result in only ligand-centered redox changes.39–41 Another situation that illustrates this redox flexibility is the case of tandem redox state changes for the metal and the ligand. This has been used in effecting multi-electron redox processes, such as the activation of dinitrogen.42 One consequence of this proclivity of RNI ligands to undergo redox processes is the ready formation of ligand-localized radicals. The stability of these ligand 1 radicals is highly system-dependent, as some complexes are isolable while others suffer from reactivity expected of radicals, such as C-C coupling and hydrogen atom transfer (HAT). Previous work in our group on ligands bearing pyridine-imine (PI) moieties has illustrated each of these scenarios. In one example of a nickel complex bearing a tetradentate bis(pyridine-imine) ligand, it was shown that 5 oxidation states were accessible (Figure 1.1A).37 Despite the formulation of two of the species as pyridine-imine radicals, the compounds were persistent and exhibited no reactivity with radical reagents. In another example from our group, the generation of a putative iron PI radical intermediate resulted in an inter-ligand C-C coupling reaction (Figure 1.1B).38 Figure 1.1. Previous examples from the group involving pyridine-imine-containing ligands. In order to further explore the reactivity of the PI ligand framework, we sought to synthesize bis(pyridine-enamide) complexes of the first row transition metals. We were interested in whether treating these complexes with hydrogen atom sources would give the bis(pyridine-imine) transition metal complexes, analogs of which have 2 been reported by Wieghardt and co-workers.33 While we were unable to observe the desired HAT reactivity, we report an intraligand C-C coupling reaction to form an indolamide ligand. Surprisingly, this reaction was shown to be operative for the corresponding lithium pyridine enamide complexes as well, and a combined experimental and computational study was undertaken to elucidate the mechanism. 3 Results and Discussion 1.1 Synthesis of Alkali Metal and Transition Metal Pyridine Enamide Complexes The synthesis of several pyridine imines was achieved through acid-catalyzed condensation of 2-acetylpyridine with o-substituted or 2,6-disubstituted anilines in toluene, with removal of water using a Dean-Stark trap (Scheme 1.1). Distillation or crystallization afforded the imines as yellow oils or solids in 52-82% yields. The corresponding potassium and lithium pyridine enamides were easily accessible in 8698% yields by treatment of the pyridine imines with KH and lithium hexamethyldisilazide (LiHMDS), respectively. Scheme 1.1. Synthesis of Li and K pyridine enamides and the parent pyridine imines. A salt metathesis route was employed for the synthesis of the first row transition metal complexes (Scheme 1.2). Treatment of CrCl2(THF), MnCl2, and 4 FeBr2(THF)2 with 2 equiv. (pyEA-AriPr2)K in THF gave the bis(pyridine enamide) complexes, (pyEA-AriPr2)2M (1-M, M = Cr, Mn, Fe) in 61-68 % yields. All compounds were shown to be high spin in solution, as determined by Evans’ method, with μeff values of 4.7(1), 5.5(1), and 5.2(1) μB for 1-Cr, 1-Mn, and 1-Fe, respectively. Scheme 1.2. Synthesis of 1-M (M = Cr, Mn, Fe, Co-py) and 2. Curiously, when CoCl2 or CoCl2(thf)2 was treated with 2 equiv. (pyEAAriPr2)K in THF, the expected (pyEA-AriPr2)2Co complex was not observed. Instead, a mixture of products was obtained, including a red diamagnetic compound, 2, in low 5 yield (7 %). The isolation of 2 was made possible by its relative insolubility in pentane compared to the other paramagnetic products formed under the reaction conditions. Based on the 1H NMR observation of four inequivalent isopropyl methyl groups, the most likely candidates were rigid Co(I) or Co(III) complexes. X-ray diffraction studies (vide infra) confirmed its identity as a Co(III) complex with three bidentate ligands. Most notably, the pyridine-enamide had undergone linkage isomerization to give a κ-N,C-pyridine-iminoalkyl ligand. 2 is a rare example of a Co(III) trialkyl coordination complex. Efforts to improve the yield of 2, including using CoBr2 as the metal precursor, substituting (pyEA-AriPr2)Li for (pyEA-AriPr2)K, and carrying out the reaction in different solvents, were ultimately unsuccessful and often resulted in no formation of compound 2. Though efforts to generate (pyEA-AriPr2)2Co proved fruitless, when CoCl2py4 was treated with 2 equiv. (pyEA-AriPr2)K in Et2O, formation of the pyridine adduct (pyEA-AriPr2)2Copy (1-Co-py) as a brick red solid in 57 % yield was observed. The solution magnetic moment was determined to be 3.9(1) μB, consistent with a high spin Co(II) complex. The last efforts to generate first row transition metal pyridine-enamide complexes focused on nickel. Unfortunately, when NiCl2 or NiCl2(DME)2 was treated with 2 equiv. (pyEA-AriPr2)K or 2 equiv. (pyEA-AriPr2)Li in THF, an intractable mixture was obtained, the major product being the parent pyridine imine. This result points to reduction of the nickel halide by the alkali-metal enamide. The resultant organic radical can then abstract a hydrogen atom from another species in solution, e.g. THF or DME, to give the free pyridine imine. 6 1.2. X-Ray Crystal Structures of 1-Fe and 1-Co-py Crystals of 1-Fe suitable for X-ray diffraction studies were obtained by slow evaporation of a concentrated Et2O/hexanes solution. The structure of 1-Fe is shown in Figure 1.2, with relevant bond metrics and angles included. Other data acquisition and refinement information is shown in Table 1.1. The geometry about Fe is distorted tetrahedral, largely due to the small bite angle of the bidentate pyridine enamide ligand (av. 79.5(2)°). This distortion allows the 2,6-diisopropylphenylamide groups to be splayed out to 136.70(7)°, minimizing steric repulsion. The Fe-Nam distances (av. 1.948(7) Å) are expectedly shorter than the Fe-Npy distances (av. 2.114(12) Å) and fall in the range of typical distances for high spin ferrous complexes. Figure 1.2. Molecular view of (pyEA-AriPr2)2Fe (1-Fe) and selected interatomic distances (Å) and angles (°): Fe1-N1, 2.1050(17); Fe1-N2, 1.9532(16); Fe1-N3, 2.1221(17); Fe1-N4, 1.9427(15); N1-C5, 1.342(3); C5-C6, 1.489(3); C6-C7, 1.340(3); N2-C6, 1.374(3); N2-C8, 1.429(2); N3-C24, 1.348(3); C24-C25, 1.482(3); C25-C26, 1.345(3); N4-C25, 1.374(3); N4-C27, 1.425(2); N1-Fe1-N2, 79.66(7); N1-Fe1-N3, 100.94(7); N1-Fe1-N4, 128.05(7); N2-Fe1-N3, 133.07(7); N2-Fe1-N4, 136.70(7); N3- Fe1-N4, 79.37(6). 7 Figure 1.3. Molecular view of (pyEA-AriPr2)2Copy (1-Co-py) and selected interatomic distances (Å) and angles (°): Co-N1, 2.1864(10); Co-N2, 1.9648(10); CoN3, 2.1802(10); Co-N4, 1.9709(10); Co-N5, 2.1148(11); N2-C6, 1.3718(16); C6-C7, 1.356(2); C5-C6, 1.4881(18); N1-C5, 1.3481(16); N4-C25, 1.3750(15); C25-C26, 1.3566(18); C24-C25, 1.4878(18); N3-C24, 1.3467(16); N1-Co-N2, 77.95(4); N1-CoN3, 172.64(4); N1-Co-N4, 99.55(4); N1-Co-N5, 93.48(4); N2-Co-N3, 99.05(4); N2Co-N4, 135.83(4); N2-Co-N5, 110.55(4); N3-Co-N4, 77.83(4); N3-Co-N5, 93.87(4); N4-Co-N5, 113.61(4); N2-C6-C7, 126.65(13); N2-C6-C5, 113.28(11); C5-C6-C7, 120.06(13); N4-C25-C26, 126.60(12); N4-C25-C24, 113.17(10); C24-C25-C26, 120.23(12). Crystals of 1-Co-py suitable for X-ray crystal structure determination were obtained by slow evaporation of a concentrated Et2O/hexanes solution. The structure is shown in Figure 1.3, with select bond distances and angles given. 1-Co-py is a C2- symmetric molecule which adopts a pseudo trigonal bipyramidal structure in the solid state. Bulky 2,6-diisopropylphenylamide groups occupy the equatorial positions with pyridine, while chelating pyridines occupy axial sites. The moderate deviation from three-fold symmetry in the equatorial plane allows for a similarly large amide separation (135.83(4)°) as in 1-Fe. The average pyridine-enamide bite angle, 8 77.91(11)°, is slightly smaller than in 1-Fe. Co-N bond distances are 1.968(4) Å (ave.) for the amides, 2.183(4) Å (ave.) for chelate pyridines, and 2.1148(11) Å for the unique pyridine, all in the range of expected distances for high spin Co(II) complexes. Table 1.1. Select Crystallographic and Refinement Data for (pyEA-AriPr2)2Fe (1-Fe), (pyEA-AriPr2)2Copy (1-Co-py), (κ-C,N-pyEA-AriPr2)3Co (2), and {κ-N,N-N(C6H3(2iPr)CMe2C(Me)(2-py))}2Co (3-Co). 1-Fe formula formula wt C38H46N4Fe 614.64 space group Z P21/n 4 a, Å 12.0967(8) b, Å 14.8011(11) c, Å α, deg β, deg γ, deg V, Å3 ρcalc, g.cm-3 µ, mm-1 20.1037(14) 90 107.236(3) 90 3437.8(4) 1.188 0.469 temp, K λ (Å) 213(2) 0.71073 Reflections Collected 33825 Independent Reflections 8532 R(int) 0.0366 R indices [I > 2σ(I)]b,c R1 = 0.0463 wR2 = 0.1109 R indices (all data)b,c GOFd R1 = 0.0786 wR2 = 0.1267 1.022 Crystal size (mm3) 0.45 x 0.30 x 0.05 1-Co-pya C47H61N5OCo 770.94 P21/n 4 11.3721(5) 23.8329(11) 16.3006(7) 90 101.587(2) 90 4327.9(3) 1.183 0.436 203(2) 0.71073 50176 13192 0.0290 R1 = 0.0370 wR2 = 0.0923 R1 = 0.0539 wR2 = 0.1015 1.012 0.60 x 0.60 x 0.60 2 C60H72N6Co 936.17 R̅ 6 19.691(2) 19.691(2) 24.631(3) 90 90 120 8271.2(16) 1.128 0.353 203(2) 0.71073 3-Co C38H46N4Co 617.72 P̅ 4 9.7996(7) 9.8387(7) 38.267(3) 87.205(4) 83.381(4) 89.069(4) 3660.3(5) 1.121 0.498 173(2) 0.71073 10193 51444 3141 0.0459 R1 = 0.0508 wR2 = 0.1193 R1 = 0.1254 wR2 = 0.1710 1.067 0.35 x 0.20 x 0.10 12049 0.0349 R1 = 0.0598 wR2 = 0.1251 R1 = 0.0702 wR2 = 0.1287 1.166 0.35 x 0.20 x 0.05 aContains Et2O of solvation. bR1 =ΣFo| - |Fc||/Σ|Fo|. cwR2 = [Σw(|Fo| - |Fc|)2/ΣwFo2]1/2. dGOF (all data) = [Σw(|Fo| - |Fc|)2/(n - p)]1/2, n = number of independent reflections, p = number of parameters. 9 1.3. X-Ray Crystal Structure and UV-Vis of 2 Figure 1.4. Molecular view of (κ-C,N-pyEA-AriPr2)3Co (2), whose isopropyl methyl groups have been removed for clarity, and selected interatomic distances (Å) and angles (°): Co1-N1, 2.001(3); Co1-C6, 1.963(4); N1-C5, 1.342(5); N1-C1, 1.365(4); C1-C7, 1.476(5); C6-C7, 1.502(5); N2-C7, 1.282(4); N1-Co1-N1, 95.80(11); C6-Co1C6, 89.30(18); N1-Co1-C6 (bite angle), 89.39(16); N1-Co1-C6, 85.37(14); N1-Co1C6, 174.53(17); Co1-N1-C1, 114.6(2); N1-C1-C7, 114.3(3); C1-C7-N2, 117.0(3); C1- C7-C6, 115.5(3); C6-C7-N2, 127.5(3); Co1-C6-C7, 109.8(3). X-ray quality crystals of 2 were grown by slow evaporation of a concentrated benzene solution. 2 crystallizes in the highly symmetric R̅ space group, with one ligand per asymmetric unit. The structure of 2 is shown in Figure 1.4, accompanied by relevant bond distances and angles. 2 adopts a C3-symmetric paddlewheel structure and co-crystallizes with one molecule of benzene, which lies along the C3 rotation axis. With bite angles of 89.39(16)° and inter-ligand angles of 95.80(11)° (NCoN), 89.30(18)° (CCoC), and 174.53(17)° (NCoC), the molecule is nearly octahedral. The 10 Co-C distance of 1.963(4) Å and Co-Npy distance of 2.001(3) Å are consistent with a low spin Co(III) complex. The paucity of trialkyl Co(III) complexes makes the formation of 2 noteworthy. While Klein’s Co(PMe3)3Me343 and Chirik’s (PNP)CoMe327 have been characterized by NMR spectroscopy, 2 is the first crystallographically characterized tris(sp3-alkyl) cobalt(III) complex. This is in contrast to the several examples of Co(III) complexes with multiple anionic sp- and sp2-hybridized carbon donors which have been crystallographically characterized, including tris(κ-C,N-2phenylpyridine)cobalt44 and Long’s Li3[Co(CCSiMe3)6].45 The mechanism of formation of 2 is currently unknown. The low yield of 2, as well as the presence of several other unidentified products, makes a mechanistic proposal dubious. One possible pathway for the formation of 2 is the initial formation of a tris(pyridine-enamide) Co(II) anion, which could undergo disproportionation to a Co(I) complex and compound 2. This pathway is well-documented, as several cobalt(III) complexes have been generated via reaction of cobalt(II) halides with aryllithium and aryl magnesium reagents.44,46–48 These complexes are also similarly generated in low yield. Given the near-octahedral geometry of compound 2, a UV-Vis spectrum was recorded in order to determine the ligand field parameters, Δo and B (Figure 1.5). The major bands at 370 and 493 nm (27,000 and 20,000 cm-1, respectively) are assigned as d-d transitions. The large extinction coefficients of these absorptions are likely a consequence of intensity stealing from the broad charge transfer band that trails out into the visible region. The d6 Tanabe-Sugano diagram was employed to fit the 493 11 nm and 370 nm bands to the 1A1→1T1 and 1A1→1T2 transitions. For a Δ/B value of 45, Δo and B were determined to be 22,000 cm-1 and 481 cm-1, respectively. This value for B is 44% of the free ion value for Co3+ (1100 cm-1) and indicates a large degree of covalency, which is expected for a complex with the three M-C bonds. In order to assess the ligand field strength imparted by the alkyl ligands, the rule of average environment was used. Given that Co(py)63+ is estimated to have a Δo of ~ 24,000 cm-1,49 the expected Δo for CoR63- is ~ 20,000 cm-1. This value is significantly smaller than that of Co(CCSiMe3)63-, which was determined by Berben and Long to have a Δo of 32,500 cm-1.45 One possible explanation is that Co(CCSiMe3)63- has shorter Co-C bonds than 3 (1.908(3) Å vs. 1.963(4) Å), resulting in greater orbital overlap and a larger Δo. Figure 1.5. UV-Vis spectrum of 2 in THF. Concentrations are 10 μM (blue), 100 μM (red), and 200 μM (green). 12 1.4. Hydrogen Atom Transfer Reactivity with 1-Fe In order to determine the viability of HAT to transition metal pyridine-enamide complexes, DFT calculations were conducted for the reaction of 1-Fe and a cobalt analog, 1’-Co, with hydrogen atom sources (Scheme 1.3). For the hypothetical twostep HAT reaction of 1-Fe with H2, both steps were calculated to be slightly favorable, with a ΔGcalc of -7.2 kcal/mol and -2.4 kcal/mol, respectively. Likewise, the reaction of H2 with the cobalt analog, 1’-Co, was shown to be favorable overall (ΔGcalc = -6.8 kcal/mol), despite a slightly unfavorable second HAT step (ΔGcalc = 3.1 kcal/mol). To test the calculations, 1-Fe was treated with H2, dihydroanthracene, and nBu3SnH (Scheme 1.4). No reaction was observed with the reagents at room temperature, and heating resulted in decomposition, with no new clean products observed by 1H NMR spectroscopy. Scheme 1.3. Calculated thermodynamic parameters for the reaction of 1-M with H2. In addition to these H2 sources, 1-Fe was also treated with tert-butyliodide in benzene (Scheme 1.4). A color change from dark red to olive green was observed, and several paramagnetic products were formed, as confirmed by NMR analysis. When the reaction was conducted in a sealed tube, isobutylene was observed by 1H 13 NMR spectroscopy. One potential route for isobutylene formation is homolytic C-I bond cleavage of tBuI to give an Fe(III) iodide species and tert-butyl radical. The tertbutyl radical could then undergo HAT to the enamide alkene to generate isobutylene and an Fe(III) complex containing a PI radical, or, depending on the preferred electronic state, an Fe(II) complex bearing a neutral PI ligand. This five-coordinate compound could then dimerize, which could form different isomers, explaining the complex mixture of products observed. Unfortunately, crystallization of the product was unsuccessful, so definitive assignments of the products proved elusive. Scheme 1.4. Reactions of 1-Fe with H2, nBu3SnH, dihydroanthracene, and tBuI. 14 1.5. Thermolysis of Transition Metal and Alkali Metal Enamides In the course of reactivity studies for 1-M, the thermal stability of the complexes was investigated. When 1-Co-py was heated at 140 °C in C6D6 for 36 h, a slight color change from dark red-brown to dark red was observed. The formation of Scheme 1.5. Thermolyses and aqueous quench of 1-M (M = Cr, Mn, Fe, Co-py). two paramagnetic products in a 9:1 ratio was observed by 1H NMR. The major product was shown by X-ray diffraction studies (vide infra) to be {κ-N,N-N(C6H3)(2iPr)CMe2C(Me)(2-py))}2Co (3-Co), the result of the formal addition of the isopropyl C-H bond across the enamide alkene, affording two new anionic pyridyl indolamide ligands, with concomitant loss of pyridine (Scheme 1.5). The free indoline was 15 obtained via an aqueous quench. Likewise, the thermolyses of 1-M (M = Cr, Mn, Fe), followed by an aqueous quench, gave a mixture of parent pyridine-imine and the indoline in different ratios depending on the transition metal. The quench of 1-Cr gave an indoline:PI ratio of 5:1, while the ratios obtained for 1-Mn and 1-Fe were 4:1 and 0.8:1, respectively. It can be assumed that the analogous 3-M (M = Cr, Mn, Fe) are formed in the process. Notably, this C-C coupling reaction results in the generation of a quaternary center. In order to determine whether the cyclization reaction was exclusive to transition metals, a solution of (pyEA-AriPr2)Li in benzene was heated at 160 °C for 3 days, resulting in a color change from orange to green. An aqueous quench confirmed that the same indoline formation had occurred. To test the scope of the reaction, several (pyEA-ArR,R’)Li compounds (R, R’ = Me, Et; R = H, R’ = Me) were heated in the same manner. In all cases, clean conversion to the indoline compound was observed (Eq. 1.1). The catalytic nature of the reaction was also probed (Eq. 1.2). Heating a solution of (2,6-Et2C6H3)N=C(Me)(2-py) at 140 °C in benzene with 10 mol % LiHMDS resulted in catalytic turnover (9.5 turnovers in 3 days). 16 1.6. X-ray Crystal Structure of 3-Co a. b. Figure 1.6. a) Enantiomeric {κ-N,N-N(C6H3(2-iPr)CMe2C(Me)(2-py))}2Co (3-Co (S), upper left) and (R) (lower right) molecules in the asymmetric unit. b) Molecular view of 3-Co (S), and selected interatomic distances (Å) and angles (°): Co1-N1, 2.051(3); Co1-N2, 1.908(3); Co1-N3, 2.050(3); Co1-N4, 1.907(3); N1-C5, 1.339(4); N3-C24, 1.342(4); C5-C6, 1.515(5); C24-C25, 1.524(5); C6-C14, 1.538(4); C25-C33, 1.538(5); N2-C6, 1.492(4); N4-C25, 1.481(4); N2-C13, 1.385(4); N4-C32, 1.385(4); N1-Co1-N2, 82.21(11); N1-Co1-N3, 111.37(12); N1-Co1-N4, 116.19(11); N2-Co1- N3, 116.07(12); N2-Co1-N4, 148.41(12); N3-Co1-N4, 82.44(11). Crystals of 3-Co were obtained via slow evaporation of a concentrated Et2O solution. Select bond lengths and angles are provided in Figure 1.6. 3-Co crystallizes in the P̅ space group, with 2 molecules per asymmetric unit. As mentioned above, the cyclization results in the formation of a chiral quaternary center. The crystal 17 structure reveals a racemic mixture of (S) and (R) ligand isomers, as the asymmetric unit contains both (R,R)Co and (S,S)Co stereoisomers. 3-Co has a C2-symmetric distorted tetrahedral geometry, with acute ligand bite angles of 82.21(11)° and 82.44(11)°, slightly larger than for 1-Co-py (av. 77.91(11)°). As is the case for 1-Fe and 1-Co-py, the amide nitrogen atoms are separated by a large angle (148.41(12)°), likely due to sterics. The Co-Npy and Co-Nam distances of 2.051(3) and 1.908(3) Å are again in the expected range for high spin Co(II) complexes. 1.7. Kinetics of Cyclization for (pyEA-ArR2)Li (R = Me, Et, iPr) and 1-M (M = Cr, Mn, Fe, Co-py). Figure 1.7. RǂeDaecntiootnespfreorgrroecsesnoef((ipnyteErnAa-lAsrtEant2d)aLridc).yc*lDizeantiootnesmToHniFto-dre8.d by 1H NMR. Kinetics experiments for the conversion of (pyEA-ArR2)Li (R = Me, Et, iPr) to the corresponding indolamides were conducted. The rate of disappearance of (pyEAArR2)Li was monitored by 1H NMR using ferrocene as an internal integration standard. This is illustrated in Figure 1.7 for the conversion of (pyEA-ArEt2)Li to {κ- 18 N,N-N(C6H3(2-Et)CHMeC(Me)(2-py))}Li. Table 1.2. Kinetics of (pyEA-ArRR')Li (ArRR' = 2,6-R2-C6H3 (R = iPr, Et, Me), 2Me-C6H4) and (pyEA-AriPr2)2M (1-M, M = Cr, Mn, Fe, Co-py) rearrangement to corresponding indolamides {κ-N,N-N(C6H3(2-R)CR'R"C(Me)(2-py))}Li (R = iPr, R' = R" = Me; R = Et, R' = H, R" = Me; R = Me, R' = R" = H; R = R' = R" = H) and {κN,N-N(C6H3(2-iPr)CMe2C(Me)(2-py)}2M (3-M, M = Cr, Mn, Fe, Co). Compound (pyEA-ArMe2)Lia T (°C(±1)) 100 120 130 140 150 k (× 104 s-1) 0.072(1) 0.47(1) 1.2(1) 2.7(1) 5.9(1) ΔGǂ (kcal/mol) 30.8(1) 31.0(1) 31.1(1) 31.2(1) 31.3(1) (pyEA-ArEt2)Li 130 6.3(1) 29.7(1) (pyEA-AriPr2)Li 130 0.019(1) 34.4(1) (pyEA-o-tol)Lib (py(EA-o-tol)-d5)Lib 130 0.29(1) 130 0.25(1) 32.2(1) 32.3(1) (pyEA-o-tol)Lic (py(EA-o-tol)-d3)Lic 130 0.33(1) 130 0.27(1) 32.1(1) 32.3(1) (pyEA-AriPr2)2Cr (1-Cr)d (pyEA-AriPr2)2Mn (1-Mn)d,e (pyEA-AriPr2)2Fe (1-Fe)d (pyEA-AriPr2)2Co-py (1-Co-py)d,f 130 130 130 130 130 0.040(4) - 0.06(2) 0.13(1) 0.034(6)g 33.8(1) 33.5(3) 32.8(1) 33.9(2) aFrom an Eyring plot, ΔHǂ = 26.9(2) kcal/mol, ΔSǂ = -10.3(5) cal/mol·K. bTandem runs: kH/kD5 = 1.16(9). cTandem runs: kHkD3 = 1.22(9). dAnalytical problems associated with NMR spectral integration of paramagnetic substances hampered accuracies. eOverlapping, broad resonances prevented analysis by 1H NMR integration. fFor 1-Co-py, py inhibits the rate of rearrangement, indicating that its dissociation is not rate-determining. gConducted with 10 equiv of pyridine present. When the reaction was run in C6D6, the data could not be fit to a single exponential. This could arise from the presence of different aggregation states or the influence of the product on the kinetics. When THF-d8 was used as the solvent, the reaction followed clean first-order kinetics, with rate constants given in Table 1.2. For 19 the three enamides, the rate constant decreases as Et > Me > iPr, not following an obvious steric or electronic trend. For (pyEA-ArMe2)Li, the reaction was monitored at several temperatures in the range of 100-150 °C to determine activation parameters. An Eyring analysis gave ΔHǂ = 26.9(2) kcal/mol and ΔSǂ = -10.3(5) kcal/mol·K, indicating significant bond-breaking in a somewhat ordered transition state (Figure 1.8). -0.073 -0.074 -0.075 -0.076 y = -26.929x - 0.0103 R² = 0.99983 -0.077 {ln(k/T) + ln(h/kB)}R -0.078 -0.079 -0.08 -0.081 -0.082 -0.083 0.0023 0.00235 0.0024 0.00245 0.0025 0.00255 0.0026 0.00265 0.0027 1/T (K-1) Figure 1.8. Eyring plot for the conversion of (pyEA-ArMe2)Li to {κ-N,N-N(C6H3(2Me)CH2C(Me)(2-py)}Li. Kinetics experiments for the cyclization of 1-M (M = Cr, Mn, Fe, Co-py) to 3M (M = Cr, Mn, Fe, Co) were also conducted. While the rates for the transition metal complexes were qualitatively faster than that of (pyEA-AriPr2)Li, a definitive conclusion could not be reached due to the larger error associated with these measurements. This is predominately a result of inaccurate integration of 20 paramagnetically-shifted 1H resonances, some of which span a range of several ppm. It is worth mentioning that addition of pyridine to 1-Co-py results in a rate decrease by a factor of 4. This supports a mechanism involving reversible pyridine dissociation followed by rate-determining indolamide formation (Scheme 1.6). Since no intermediate containing a single indolamide ligand is observed by 1H NMR, it can be assumed that the second ligand cyclization is faster than the first. Scheme 1.6. Proposed pathway for conversion of 1-Co-py to 3-Co. 1.8. Calculations for the Rearrangement of (pyEA-ArMe2)Li In order to probe the mechanism of the C-C bond forming cyclization, DFT calculations were performed at 130 °C (Figure 1.9). The calculations (MP2 and MO6) indicate a two-step process. In the first step, a hydrogen is transferred from the methyl 21 position to the alkene to generate an azapentadienyl intermediate. In the second step, C-C bond formation occurs to give the indolamide product. Of particular note is that C-C bond formation (TS2) has a higher overall barrier, 28.7 kcal/mol (MP2) and 35.5 kcal/mol (MO6), than the hydrogen transfer (TS1), 24.9 (MP2) and 29.7 (MO6). Also, the intermediate is high in energy (24.4 and 23.1 kcal/mol), such that C-C bond formation formally has a low barrier (4.3 and 12.4). 1.509 ‡ 1.874 N Li 1.945 N H 1.272 sp2 N Li N H intermediate 28.7/35.5 1.942 N Li 1.980 N ‡ 2.496 H ∆G° (kcal/mol) N Li N 24.9/29.7 TS1 24.4/23.1 H 18.0/17.8 sp3 2.230 N Li 2.103 N H rotamer 2.011 TS2 0.0/0.0 N Li N -11.9/-7.7 Figure 1.9. Calculations of (pyEA-ArMe2)Li rearrangement conducted at MP2 and M06 levels of theory at 403.15 K. Note that the C-C bond forming step is ratedetermining because the intermediate azapentadienyl anion is at a high energy. The calculations also indicate the formation of another intermediate in which the aryl group has rotated such that the anionic CH2 coordinates to the Li (labeled “rotamer” in Figure 1.8). This intermediate lies lower in energy than the aforementioned intermediate by 6.4 (MP2) and 5.3 kcal/mol (MO6). It bears 22 mentioning that THF, which has been omitted in these calculations, would be expected to affect the likelihood of this coordination mode, as solvent binding and reorganization would play a non-trivial role in altering the calculated energies. 1.9. Deuterium Labeling Studies The surprising computational conclusion that C-C bond formation is ratedetermining led us to pursue deuterium labeling studies. For the ease of synthesis, we substituted the o-tolyl pyridine-imines for the 2,6-dimethylphenyl pyridine-imine. (pyEA-o-tol)Li was synthesized as indicated in Scheme 1.1. Deuterium labeling of the aryl CH3 and the alkene CH2 was then targeted. (o-CD3-C6H4)N=C(Me)(2-py) was synthesized by condensation of 2-acetylpyridine and o-CD3-aniline, while (oCD3-C6H4)N=C(CD3)(2-py) was synthesized from 2-COCD3-py and o-CD3-aniline. The Li compounds (pyEA-o-tol-d3)Li and (pyEA-o-tol-d5)Li were generated in high yield by treatment with LiHMDS. With the deuterated Li salts in hand, experiments were conducted to test the computational results. In the parallel thermolyses of (pyEA-o-tol)Li and (pyEA-o-told3)Li, the KIE (kH/kD) was determined to be 1.22(9). If hydrogen transfer was ratedetermining, the expected KIE would likely be larger than the observed value, since it would be a primary isotope effect in a process with significant bond-breaking in the transition state. Moreover, an examination of the 1H and 2H NMR spectra for the thermolysis of (pyEA-o-tol-d3)Li showed H-D scrambling between the methyl CD3 and the alkene CH2. An equilibrium mixture of isotopomers was generated within the first 5 % conversion to indolamide product (Figure 1.10). This result supports 23 reversible hydrogen transfer, which is consistent with the lower calculated activation barrier to hydrogen transfer compared to C-C bond formation. Figure 1.10. Intramolecular equilibrium benzyl-vinyl H/D exchange for (pyEA-C6H4- o-CD3)Li. Resonances at 4.06 corresponds to Ph-CH3. and 3.53 ppm are *Denotes thf-d8. vinyl C-H, while 2.10 ǂDenotes ferrocene. ppm In order to determine the equilibrium isotope effect (EIE), the resonances corresponding to the alkene C(H/D)2 and methyl C(H/D)3 were integrated by 1H and 2H NMR. By 1H NMR integration, the methyl has 1.11 H atoms and the alkene has 0.89 H atoms. Similarly, by 2H NMR integration the methyl has 1.9 D atoms, while the alkene has 1.1 D atoms. Assuming a purely statistical distribution of H/D atoms across all 5 positions, one would expect the methyl to have 1.2 H and 1.8 D and the alkene to have 0.8 H and 1.2 D, which is different from the observed values, indicating an EIE. Scheme 1.7 shows the EIE analysis used, along with the relevant equilibrium 24 equations for the interconversion of isotopomers. The calculation requires an equilibrium concentration quantification for each isotopomer, where A is the CD3/CH2 starting material, B is the CD2H/CDH isotopomer formed via a single H/D exchange, and C is the CDH2/CD2 isotopomer which results from double H/D exchange. Ratios of A, B, and C are then equated to the experimentally determined ratios, thus allowing for the solution of a system of equations. From these equations, the EIE was determined to be 1.20. This calculation is based on the assumptions that secondary Scheme 1.7. EIE analysis for the thermolysis of (pyEA-C6H4-o-CD3)Li. 25 THF-d8 A CD3 130°C CD2 B CD2H is(sootlvo)Lpie N effects N are 3kf/z (solv)Li nkre/zg' ligible and N tNhat CH2D 2kr N (solv)Li the alkenekfpositions areN D indistinguishable. This value for the EIE agrees well with the computational values determined for both the z = kf(H)/kf(D) z' = kr(H)/kr(D) coz/nz' v= eKr(Hs)i/oK(nD) o=fEIAE to B and B to Cres,acrpwrraraimonhrgbitmlcoinehgntwere 1.09 and 1.08, respectively (Figure 1.11). B Note that the computations were conducted on (pyEA-ArMe2)Li, with one CD2H CDH C CDH2 methyl (solv)Li gNroup iDgnor2ekfd/z in order forNthe (solv)Li CcHaDlc2 ulatioknrs to be suitabNle (solv)Li fCoDr2comparison to N experiment. 2kr/z' N 2kf N B C EIE = KH/KD = exp[(GD - GH)/RT] EIE = 1.078 A B EIE = KH/KD = exp[(GD - GH)/RT] EIE = 1.091 Figure 1.11. EIE Computations for the thermolysis of (pyEA-C6H4-o-CD3)Li. Note: 1 a.u. = 627.51 kcal/mol. The argument for rate-determining C-C bond formation was further buttressed by the parallel thermolyses of (pyEA-o-tol)Li and (pyEA-o-tol-d5)Li (Scheme 1.8), which resulted in a KIE of 1.16(9). This value is lower than the primary isotope value 26 expected for rate-determining hydrogen transfer. The reaction is therefore comprised of a pre-equilibrium between lithium enamide and the azapentadienyl intermediate (or rotamer) followed by rate-determining C-C bond formation. KiH (solv)Li N N k fi(H) kri(H) k fr(H) 403.15 K THF-d8 MO6/6-311++G(d,p) krr(H) KrH sp2 N Li N H intermediate sp3 N Li N H rotamer kci(H) kcr(H) N (solv)Li N (solv)Li N N CD3 D D KiD5 kfi(D) kri(D) k fr(D) krr(D) KrD5 CD2 N Li CD3 intermediate N D2C N Li N rotamer CD3 kci(D) kcr(D) N (solv)Li N D D CD3 (pyEA-ArMe 2)Li rotamer intermediate G-corr 0.195542 0.196739 0.197407 E -697.369728 -697.342625 -697.334731 G -697.174186 -697.145886 -697.137324 KiH = 1.00 KiD5 (pyEA-Ar(CH3)(CD3))Li rotamer-d5 intermediate-d5 0.178447 0.179696 0.180315 -697.369728 -697.342625 -697.334731 -697.191281 -697.162929 -697.154416 KrH = 1.04 KrD5 Figure 1.12. Computational EIE analysis for the pre-equilibrium hydrogen transfer. Energies are given in kcal/mol. Figure 1.12 shows the computational ratio of equilibrium constants for the hydrogen transfer for the d0 versus d5 isotopologue. Values of 1.00 for the 27 azapentadienyl intermediate and 1.04 for the rotamer intermediate have been determined. This points to the C-C bond formation step as the source of the modest KIE observed, which is in line with a secondary isotope effect expected for carbon rehybridization in the second transition state. Scheme 1.8. Parallel experiments to determine KIE of cyclization reaction. 1.10. Comments on the Mechanism of Indoline Formation Though unexpected, the generation of the indoline via C-C bond formation has literature precedent (Scheme 1.9). Burger et al. reported the thermolysis of a (pyridine-diimine)rhodium(I)azide which afforded an indolamide rhodium(III) product.50 The reaction is proposed to proceed via formation of a terminal rhodium(III) nitride, which abstracts a hydrogen atom from the isopropyl methine C-H to give an imido. The resultant alkyl radical reacts with the imine to forge the new CC bond, followed by insertion of the imido into the remaining isopropyl methine C-H bond to give the amine-bound rhodium(I) product. Holland et al. reported a similar example in which the generation of a 28 (nacnac)iron(III) imido results in indoline formation, presumably via a hydrogen atom abstraction mechanism.51 These reactions have been proposed to be radical processes, which is attractive since both pyridine diimine (PDI) and nacnac ligands have been implicated in redox non-innocence. In one last example by Shen et al., treatment of lanthanide chloride salts with 3 equiv. Na(nacnac) results in indolamide formation via deprotonation of the methyl group followed by attack on the imine by the resultant carbanion.52 Scheme 1.9. Previous literature examples of metal-templated indolamide formation. In the present case, while calculations and experiment both support hydrogen transfer followed by C-C bond formation, the nature of the hydrogen transfer step could not be definitively determined. This is largely a consequence of the lower 29 barrier for H transfer relative to C-C bond formation, which makes the first step difficult to probe. One possibility is a HAT process, which would generate a benzylic radical and a pyridine imine radical, followed by radical coupling. This is an appealing mechanistic proposal due to the stability of metal-coordinated pyridine imine radicals. Other routes which cannot be ruled out include hydride (H-) and proton (H+) transfer events. Scheme 1.10 shows the interconversion of resonance structures formed from each pathway in order to illustrate that any of these intermediates could be formed along the reaction coordinate, regardless of the mechanism of hydrogen transfer. Scheme 1.10. Possible hydrogen transfer pathways and interconversion of resonance structures. 30 1.11. Comparison to Other Indoline Syntheses Since there are no observable byproducts in the cyclization of the lithium enamides, this is a potentially attractive route to indolines. A couple of points about the substrate scope deserve attention. When the analogous thermolysis is attempted for the substrate in which pyridine is replaced by a phenyl group, no cyclization to the indolamide is observed. Whether the pyridine is simply acting as an electronwithdrawing group is unknown, as a detailed study containing phenyl groups with electron-withdrawing substituents has not been conducted. Even if the scope is pyridine-specific, this is a viable route to pyridyl indolines, which could be used as bidentate ligand constructs. Also, the clean formation of a quaternary center makes this reaction more impactful. Efforts toward the enantioselective synthesis of these ligands could prove to be valuable. Figure 1.13. Synthesis of indolines via hydrogenation of indoles (A) and hydrogenation of 3H-indoles (B). PMHS = poly(methylhydrosiloxane). A comparison of our system to previous routes for the synthesis of indolines is 31 informative. Hydrogenation of both indoles and 3H-indoles has been used to generate indolines (Figure 1.13).53,54 Other representative examples are the Pd-catalyzed aryl C-H amination (Figure 1.14A)55 and Cu-catalyzed coupling of amines and aryl halides (Figure 1.14B).56 Notably, these cross-coupling reactions both occur via C-N bond formation, as opposed to the C-C bond formation of our system. Also, the Pdcatalyzed C-H amination requires the use of protecting groups, whereas our method does not. Figure 1.14. Indoline synthesis via Pd-catalyzed aryl C-H amination (A) and Cucatalyzed coupling (B). 32 Conclusions A series of first row transition metal pyridine-enamide complexes, 1-M (M = Cr, Mn, Fe, Co-py) was synthesized from suitable metal halide precursors and 2 equiv. (pyEA-AriPr2)K. When CoCl2 was used, a rare diamagnetic trialkyl cobalt(III) species was isolated and crystallographically characterized. Thermolysis of 1-Co-py resulted in the generation of an indolamide ligand via intra-ligand C-C bond formation. Similarly, thermolyses for 1-M (M = Cr, Mn, Fe) and (pyEA-AriPr2)Li, followed by an aqueous quench, yielded the free indoline. A combined computational and experimental study including kinetics and deuterium labeling studies supported a mechanism involving reversible hydrogen transfer followed by rate-determining C-C bond formation. While the current substrate scope for the indoline formation is narrow, the thermolysis of Li pyridine-enamides represents a novel, transition metaland byproduct-free synthesis of indolines which supplements current methods. Of particular interest is the formation of a new chiral quaternary center. 33 Experimental General considerations. All manipulations were performed using either glovebox or high vacuum line techniques. All glassware was oven dried. THF and ether were distilled under nitrogen from purple sodium benzophenone ketyl and vacuum transferred from the same prior to use. Hydrocarbon solvents were treated in the same manner with the addition of 1-2 mL/L tetraglyme. Benzene-d6 and was dried over sodium, vacuum transferred and stored over sodium. THF-d8 was dried over sodium and vacuum transferred from sodium benzophenone ketyl prior to use. Fe{N(TMS)2}2(THF) was prepared according to a literature procedure. Lithium bis(trimethylsilyl)amide was purchased from Aldrich and recrystallized from hexanes prior to use. All other chemicals were commercially available and used as received. NMR spectra were obtained using an INOVA 400 MHz and 500 MHz spectrometers. Chemical shifts are reported relative to benzene-d6 (1H δ 7.16; 13C{1H} δ 128.39) and THF-d8 (1H δ 3.58; 13C{1H} δ 67.57). Multidimensional techniques were conducted using INOVA software affiliated with the spectrometers. Magnetic measurements obtained in solution were conducted via Evans' method in benzene-d6. Elemental analyses were performed by Complete Analysis Laboratories, Inc. (E & R Microanalytical Division), Parsippany, New Jersey. Procedures. 1. (2,6-iPr2C6H3)N=C(Me)(2-py). A 100 mL flask adapted with Dean-Stark trap was charged with 2,6-diisopropylaniline (9.66 g, 54.5 mmol), 2-acetylpyridine (6.60 g, 54.5 mmol), TsOH·H2O (259 mg, 1.36 mmol), and 36 mL toluene. The pale yellow solution was refluxed for 4.5 h as water was collected in the trap. The volatiles 34 were removed in vacuo to afford a dark orange oil, to which CH2Cl2 (40 mL) and sat. NaHCO3 (aq, 20 mL) were added. The layers were separated and the aqueous layer was extracted with CH2Cl2 (2 x 20 mL). The combined organic extracts were dried over MgSO4, filtered, and the solvent was removed in vacuo. The resulting crude light brown solid was purified by crystallization from hot hexanes to produce 9.59 g of light yellow crystals (63% yield). 1H NMR (CDCl3): δ 1.15(d, 12H, 7 Hz), 2.22 (s, 3H), 2.75 (sept, 2H, 7 Hz), 7.10 (m, 1H), 7.19 (m, 2H), 7.39 (ddd, 1H, 7 Hz, 5 Hz, 1 Hz), 7.82 (td, 1H, 8 Hz, 2 Hz), 8.36 (dt, 1H, 8 Hz, 1 Hz), 8.69 (ddd, 1H, 5 Hz, 2 Hz, 1 Hz). 13C NMR (CDCl3): δ 17.46, 23.04, 23.37, 28.39, 121.45, 123.11, 123.70, 124.91, 135.91, 136.60, 146.55, 148.72, 156.61, 167.08. 2. (2,6-Et2C6H3)N=C(Me)(2-py). A 50 mL flask adapted with Dean-Stark trap was charged with 2,6-diethylaniline (2.97 g, 19.9 mmol), 2-acetylpyridine (2.42 g, 20.0 mmol), TsOH·H2O (0.18 g, 0.95 mmol), and 12 mL toluene. The yellow solution was heated at reflux for 16 h as water was collected via the trap. Volatiles were removed in vacuo to give an orange oil, to which CH2Cl2 (20 mL) and sat. NaHCO3(aq) (20 mL) were added. The layers were separated and the aqueous layer was extracted with CH2Cl2 (2 x 20 mL). The combined organic extracts were dried over MgSO4, filtered, and the solvent was removed in vacuo. The crude oil was purified by vacuum distillation to afford a yellow oil (4.13 g, 82.4 %). 1H NMR (CDCl3): δ 1.13 (6H, t, 7.5 Hz, Et CH3), 2.19 (3H, s, Im CH3), 2.37 (4H, m, Et CH2), 7.03 (1H, m, Ph C-H), 7.11 (2H, m, Ph C-H), 7.39 (1H, ddd, 8 Hz, 5 Hz, 1 Hz, py CH), 7.81 (1H, td, 8 Hz, 2 Hz, py C-H), 8.36 (1H, d, 8 Hz, py C-H), 8.68 (1H, d, 5 Hz, py C-H). 13C NMR (CDCl3): δ 13.84, 17.12, 24.70, 121.38, 123.43, 124.92, 126.04, 35 131.28, 136.58, 147.86, 148.70, 156.58, 167.02. 3. (2,6-Me2C6H3)N=C(Me)(2-py). A 50 mL flask adapted with Dean-Stark trap was charged with 2,6-dimethylaniline (1.53 g, 12.6 mmol), 2-acetylpyridine (1.52 g, 12.6 mmol), TsOH·H2O (0.123 g, 0.647 mmol), and 6 mL toluene. The yellow solution was heated at reflux for 16 h as water was collected via the trap. Volatiles were removed in vacuo to give a light brown oil. Vacuum distillation produced 2.10 g (71%) of a light orange oil. 1H NMR (CDCl3): δ 2.03 (s, 6H, Ph CH3), 2.18 (s, 3H, Im CH3), 6.97-6.89 (m, 1H, Ph C-H), 7.10-7.02 (m, 2H, Ph C-H), 7.39 (dd, 1H, 7 Hz, 5 Hz, py C-H), 7.81 (t, 1H, 8 Hz, py C-H), 8.37 (d, 1H, 7.5 Hz, py C-H), 8.67 (d, 1H, 5 Hz, py C-H). 13C NMR (CDCl3): δ 16.74, 18.04, 121.38, 123.12, 124.94, 125.49, 127.98, 136.54, 148.67, 148.80, 156.53, 167.29. 4. (o-tolyl)N=C(Me)(2-py). A 25 mL flask was charged with 2-methylaniline (1.354 g, 12.6 mmol), 2-acetylpyridine (1.54 g, 12.7 mmol), TsOH·H2O (0.123 g, 0.647 mmol), and toluene (7 mL). The mixture was equipped with a Dean-Stark trap and heated at reflux for 1.5 h. Volatiles were removed in vacuo to give a red-orange oil. The residue was purified by vacuum distillation to afford a yellow oil (1.375 g, 51.9 %). 1H NMR (CDCl3): δ 2.12 (3H, s, Ph-CH3), 2.30 (3H, s, Im CH3), 6.68 (1H, d, 8 Hz, Ph), 7.03 (1H, td, 8 Hz, 1 Hz, Ph), 7.17-7.25 (m, 2H, Ph), 7.37 (1H, ddd, 7 Hz, 5 Hz, 1 Hz, py), 7.79 (1H, td, 7.5 Hz, 2 Hz, py), 8.33 (1H, dt, 8 Hz, 1 Hz, py), 8.67 (1H, ddd, 5 Hz, 2 Hz, 1 Hz, py). 13C NMR (CDCl3): δ 16.60, 17.87, 118.22, 121.45, 123.68, 124.86, 126.49, 127.12, 130.48, 136.48, 148.63, 150.02, 156.78, 166.91. 5. o-CD3-aniline. A three-neck flask equipped with a reflux condenser was 36 charged with AlCl3 (4.46 g, 33.4 mmol), one solid addition finger containing LiAlD4 (1.39 g, 33.1 mmol), and another solid addition finger containing anthranilic acid (1.00 g, 7.29 mmol). The flask was cooled to 0 °C and Et2O (50 mL) was added dropwise, resulting in a dark yellow solution. LiAlD4 was added portion-wise over 30 min, resulting in a gray suspension. The mixture was warmed from 0 °C to 20 °C over 30 min, then stirred at 20 °C for 15 min. The mixture was cooled to 0 °C and anthranilic acid was added portionwise over 30 min. The mixture was then heated at reflux for 12 h, resulting in a light green solution with gray solid. The mixture was cooled to 0 °C and quenched slowly with 2M NaOH until at pH 10. The biphasic mixture was filtered to remove the white precipitate and the layers were separated. The aqueous layer was extracted with Et2O (3 x 25 mL). The combined organic extracts were dried over MgSO4, filtered, and solvent removed under reduced pressure to give a yellow liquid. The product was distilled in vacuo to afford the product as a colorless liquid (0.400 g, 49.8 % yield). 1H NMR (CDCl3): δ 3.58 (2H, br s, NH2), 6.64-6.74 (2H, m, Ar C-H), 7.00-7.07 (2H, m, Ar C-H). 6. 2-COCD3-py. A flask was charged with 2-acetylpyridine (3.00 g, 24.8 mmol), NaOH (75 mg, 1.8 mmol), and D2O (16.5 g, 824 mmol). The mixture was stirred under Ar for 24 hr, resulting in a cloudy yellow solution. The mixture was extracted with Et2O (3 x 15 mL). The organic extracts were combined, dried over MgSO4, filtered, and Et2O removed in vacuo to give a yellow oil. The 1H NMR spectrum showed incomplete deuterium incorporation, so the crude mixture was resubmitted twice according to above protocol in order to achieve >98 % deuterium incorporation. Due to the formation of an unidentified byproduct, distillation was 37 required to afford the product as a colorless liquid (1.41 g, 46.0 % yield). 1H NMR (CDCl3): δ 7.47 (1H, dd, 7 Hz, 5 Hz), 7.83 (1H, td, 7 Hz, 1 Hz), 8.04 (1H, d, 8 Hz), 8.69 (1H, d, 5 Hz). 7. (o-CD3-C6H4)N=C(Me)(2-py). A flask was charged with 2-CD3-aniline (0.200 g, 1.82 mmol), 2-acetylpyridine (0.230 g, 1.90 mmol), toluene (3 mL), and a few crystals of TsOH·H2O. The flask was equipped with a Dean-Stark trap and heated at reflux for 15 h, resulting in a yellow solution. Toluene was removed in vacuo to afford an orange oil. The product was distilled in vacuo as a yellow oil (0.367 g, 94.5 % yield). 1H NMR (CDCl3): δ 2.29 (3H, s, CH3), 6.67 (1H, dd, 7 Hz, 1 Hz, Ph C-H), 7.03 (1H, td, 7 Hz, 1 Hz, Ph C-H), 7.16-7.24 (2H, m, Ph C-H), 7.38 (1H, ddd, 7 Hz, 5 Hz, 1 Hz, py), 7.80 (1H, td, 7 Hz, 2 Hz, py), 8.32 (1H, d, 8 Hz, py), 8.67 (1H, d, 5 Hz, py). 8. (o-CD3-C6H4)N=C(CD3)(2-py). A flask was charged with 2-CD3-aniline (0.200 g, 1.82 mmol), 2-(CD3-acetyl)pyridine (0.231 g, 1.86 mmol), toluene (6 mL), and a few crystals of TsOH·H2O. The flask was equipped with a Dean-Stark trap and heated at reflux for 15 h, resulting in a dark yellow solution. The toluene was removed in vacuo to give an orange residue. 1H NMR and GC-MS showed loss of deuterium from the ketone CD3. The residue was treated with CH3OD (6.0 g, 180 mmol) and catalytic NaOH and stirred under Ar for 24 hr. Volatiles were removed in vacuo. The process was repeated 2x in order to get full deuterium (>98%) incorporation. D2O (2 mL) and CH2Cl2 (5 mL) were added and the layers separated. The aqueous layer was extracted with CH2Cl2 (3 x 5 mL). The combined organics were dried over MgSO4, filtered, and stripped to give the product as a yellow oil 38 (0.234 g, 60.1 % yield). 9. (pyEA-AriPr2)K. A flask was charged with (2,6-iPr2-C6H3)N=C(Me)(2-py) (1.61 g, 5.75 mmol) and KH (0.693 g, 17.3 mmol). THF (25 mL) was transferred, resulting in a yellow solution with undissolved KH. The mixture was stirred under Ar for 50 h. The resultant mixture was filtered to give a dark red solution, which was stripped to an oily orange solid. The residue was triturated several times with pentane to give an insoluble yellow solid, which was collected by filtration (1.82 g, 99 % yield). NMR spectra matched those reported previously.6 10. (pyEA-AriPr2)Li. To a 50 mL flask charged with (2,6-iPr2C6H3)N=C(Me)(2-py) (2.50 g, 8.92 mmol) and LiHMDS (1.49 g, 8.90 mmol) was added 35 mL pentane via vacuum transfer at -78 °C. The mixture was stirred at 23 °C for 12 h, filtered, and the precipitate was washed (5 x 5 mL) with pentane to provide an orange solid (2.53 g, 99%). 1H NMR (C6D6 w/ drop THF): δ 1.16 (6H, d, 7 Hz, iPr CH3), 1.50 (6H, d, 7 Hz, iPr CH3), 3.58 (1H, s, alkene C-H), 3.64 (2H, sept, 7 Hz, iPr C-H), 4.38 (1H, s, alkene C-H), 6.51 (1H, m, py C-H), 6.95 (1H, td, 8 Hz, 2 Hz, py CH), 7.18 (1H, t, 7.5 Hz, Ph C-H), 7.32 (2H, d, 7.5 Hz, Ph C-H), 7.72 (1H, br s, py CH), 7.87 (1H, d, 8 Hz, py C-H). 13C NMR (THF-d8): δ 25.24, 26.02, 28.28, 71.69, 120.55, 121.48, 122.02, 123.08, 136.25, 144.14, 146.98, 154.86, 157.78, 164.18. 11. (pyEA-ArEt2)Li. A solution of LiHMDS (0.497 g, 2.97 mmol) in hexanes (10 mL) was added dropwise to a solution of (2,6-Et2-C6H3)N=C(Me)(2-py) (0.755 g, 2.99 mmol) in hexanes (10 mL), resulting in the formation of a yelloworange precipitate. Stirring was continued at 23 °C overnight. The mixture was filtered and washed 5 times with hexanes to give a light orange solid (0.693 g, 90 %). 39 1H NMR (C6D6/THF-d8): δ 1.36 (6H, t, 8 Hz, Et CH3), 2.70 (2H, m, Et CH2), 3.04 (2H, m, Et CH2), 3.64 (1H, s, alkene C-H), 4.34 (1H, s, alkene C-H), 6.54(1H, t, 6 Hz, py C-H), 7.02(1H, t, 8 Hz, py C-H), 7.19 (1H, t, 7.5 Hz, Ph C-H), 7.34 (2H, d, 7.5 Hz, Ph C-H), 7.48 (1H, d, 4 Hz, py C-H), 7.83 (1H, d, 8 Hz, py C-H). 13C NMR (C6D6/THF-d8): δ 15.28, 24.51, 75.47, 120.88, 121.15, 121.66, 125.94, 136.14, 139.15, 146.54, 154.50, 157.08, 163.59. 12. (pyEA-ArMe2)Li. A solution of LiHMDS (0.743 g, 4.44 mmol) in hexanes (10 mL) was added dropwise to a solution of (2,6-Me2-C6H3)N=C(Me)(2-py) (0.998 g, 4.45 mmol) in hexanes (10 mL), resulting in the formation of a green solid. Stirring was continued at 23 °C overnight. The mixture was filtered and washed with hexanes to give a light green solid (0.903 g, 88 % yield). 1H NMR (C6D6/THF-d8,): δ 2.36 (6H, s, CH3), 3.69(1H, s, alkene C-H), 4.29 (1H, s, alkene C-H), 6.42 (1H, m, py C-H), 6.96 (1H, t, 8 Hz, py C-H), 7.02 (1H, t, 8 Hz, Ph C-H), 7.20 (2H, d, 7 Hz Ph CH), 7.26 (1H, br s, py C-H), 7.70 (1H, d, 8.5 Hz, py C-H). 13C{1H} NMR (C6D6/THFd8): δ 18.86, 121.07, 121.25, 121.54, 128.95, 133.80, 136.32, 146.82, 154.85, 158.28, 163.48. 13C{1H} NMR (THF-d8): δ 19.32, 69.34, 119.04, 121.40, 121.94, 128.09, 132.90, 136.23, 147.07, 154.24, 156.89, 164.28. 13. (pyEA-o-tol)Li. A 50 mL flask was charged with (o-MeC6H4)N=(Me)(2-py) (500 mg, 2.38 mmol). Pentane (15 mL) was transferred to the flask in vacuo. The mixture was warmed to 0 °C, resulting in a yellow solution. Under Ar counter-flow, a solution of LiHMDS (398 mg, 2.38 mmol) in pentane (10 mL) was added dropwise, resulting in the formation of an orange precipitate. The mixture was allowed to warm to 20 °C and stirred for 12 h. The resultant mixture was 40 filtered and washed with pentane (5x 10 mL) to afford the product as a light green solid (444 mg, 86.1 %). 1H NMR (thf-d8): δ 2.13 (3H, s, CH3), 3.52 (1H, s, vy C-H), 4.05 (1H, s, vy C-H), 6.43 (1H, t, 7 Hz, Ph C-H), 6.84 (1H, t, 7 Hz, Ph C-H), 6.92 (1H, d, 7 Hz, Ph C-H), 7.06 (1H, d, 8 Hz, Ph C-H), 7.10 (1H, dd, 7 Hz, 5 Hz, py C-H), 7.61 (1H, td, 8 Hz, 2 Hz, py C-H), 7.93 (1H, d, 8 Hz, py C-H), 8.31 (1H, d, 5 Hz, py C-H). 13C NMR (THF-d8): δ 19.56, 73.03, 117.15, 121.59, 122.01, 124.53, 126.36, 130.59, 131.56, 136.53, 147.15, 155.80, 158.41, 164.91. 14. (pyEA-C6H4-o-CD3)Li. (o-Me-C6H4)N=(Me)(2-py) (395 mg, 1.85 mmol) and hexanes (10 mL) were added to a 50 mL rb flask, resulting in a yellow solution. The solution was cooled to 0 °C. Under Ar counter-flow, a solution of LiHMDS (313 mg, 1.87 mmol) in hexanes (10 mL) was added dropwise, resulting in an orange suspension. The mixture was stirred for 12 h, then filtered and washed with hexanes (3x 10 mL) to give a light pink solid (229 mg, 56.2 %). 1H NMR (thf-d8): δ 3.52 (1H, s, vy C-H), 4.05 (1H, s, vy C-H), 6.43 (1H, t, 7 Hz, Ph C-H), 6.84 (1H, t, 7 Hz, Ph CH), 6.92 (1H, d, 7 Hz, Ph C-H), 7.06 (1H, d, 8 Hz, Ph C-H), 7.10 (1H, dd, 7 Hz, 5 Hz, py C-H), 7.61 (1H, t, 8 Hz, py C-H), 7.93 (1H, d, 8 Hz, py C-H), 8.31 (1H, d, 5 Hz, py C-H). 15. {(2-py)C(=CD2)N(o-CD3-C6H4)}Li. (o-CD3-C6H4)N=(CD3)(2-py) (243 mg, 1.13 mmol) and hexanes (10 mL) were added to a 50 mL flask, resulting in a yellow solution. The solution was cooled to 0 °C. Under Ar counter-flow, a solution of LiHMDS (188 mg, 1.12 mmol) was added dropwise, resulting in an orange suspension. After stirring for 12 h, the mixture was filtered and washed with hexanes (5x 10 mL) to give a gray solid (185 mg, 74.6 %). 1H NMR (thf-d8): δ 6.42 (1H, t, 7 41 Hz, Ph C-H), 6.84 (1H, t, 7.5 Hz, Ph C-H), 6.91 (1H, d, 7 Hz, Ph C-H), 7.07 (1H, d, 8 Hz, Ph C-H), 7.09 (1H, dd, 7 Hz, 5 Hz, py C-H), 7.61 (1H, t, 7.5 Hz, py C-H), 7.93 (1H, d, 8 Hz, py C-H), 8.31 (1H, d, 5 Hz, py C-H). 16. (pyEA-AriPr2)2Cr (1-Cr). To a flask charged with (pyEA-AriPr2)K (200 mg, 0.628 mmol) and CrCl2(THF) (61 mg, 0.31 mmol) was added 12 mL THF via vacuum transfer. The mixture was allowed to warm from -78 °C to 23 °C, and stirred for 12 h. The green-brown solution was stripped to a dark green residue, pentane (15 mL) was added, and the mixture was filtered. The filter cake was washed with pentane until the filtrate was colorless, and solvent was removed to give an olive green solid (131 mg, 68% yield). Analytically pure dark green crystals were grown via slow evaporation of a concentrated Et2O/hexanes solution. 1H NMR (C6D6): δ -55.74 (ν1/2 = 1202 Hz), 8.31 (ν1/2 = 494 Hz), 9.95 (ν1/2 = 386 Hz), 10.58 (ν1/2 = 278 Hz), 26.36 (ν1/2 =1076 Hz), 28.09 (ν1/2 = 766 Hz). μeff (Evans) = 4.7(1) μB. Anal. for C38H46CrN4 (calc.) C 74.72, H 7.59, N 9.17; (found) C 74.62, H 7.77, N 9.22. 17. (pyEA-AriPr2)2Mn (1-Mn). To a flask charged with (pyEA-AriPr2)K (597 mg, 1.87 mmol) and MnCl2 (118 mg, 0.938 mmol) was added 20 mL THF (20 mL) via vacuum transfer. The mixture was allowed to warm from -78 °C to 20 °C, and stirred for 12 h. The dark orange solution was stripped to a dark yellow solid, pentane (15 mL) was added, and the mixture was filtered and washed several times with pentane. Solvent was removed from filtrate to give a yellow solid (352 mg, 61 % yield). Analytically pure red crystals were obtained by slow evaporation of a concentrated Et2O/hexanes solution. 1H NMR (C6D6): δ -17.39 (ν1/2 = 3120 Hz), 8.95 (ν1/2 = 1240 Hz), 21.12 (ν1/2 = 1330 Hz). μeff (Evans) = 5.5(1) μB. Anal. for 42 C38H46MnN4 (calc.) C 74.37, H 7.55, N 9.13; (found) C 74.19, H 7.62, N 9.28. 18. (pyEA-AriPr2)2Fe (1-Fe). To a flask charged with FeBr2(THF)2 (618 mg, 1.72 mmol) and (pyEA-AriPr2)K (1.096 g, 3.44 mmol) was transferred 35 mL THF (35 mL) via vacuum transfer. The mixture was allowed to warm from -78 °C to 20 °C over 3 h, and stirred for an additional 12 h. Volatiles were removed to give a redbrown residue. Pentane (30 mL) was added and the resultant mixture was filtered, and the filter cake was washed repeatedly with pentane. Evaporation of solvent gave 2-Fe as a brick red solid (640 mg, 61 %). Crystals suitable for X-ray diffraction were obtained via slow evaporation of a concentrated hexanes/Et2O (4:1) solution. 1H NMR (C6D6): δ -119.74 (ν1/2 = 362 Hz), -84.45 (ν1/2 = 334 Hz), -52.99 (ν1/2 = 920 Hz), -38.69 (ν1/2 = 75 Hz), -29.26 (ν1/2 = 749 Hz), 4.41 (ν1/2 = 358 Hz), 17.63 (ν1/2 =568 Hz), 19.42 (ν1/2 = 467 Hz), 27.98 (ν1/2 = 398 Hz), 39.35 (ν1/2 = 95 Hz), 42.53 (ν1/2 = 74 Hz), 104.91 (ν1/2 = 465 Hz), 117.54 (ν1/2 = 997 Hz). μeff (Evans) = 5.2(1) μB. Anal. for C38H46FeN4 (calc.) C 74.26, H 7.54, N 9.12; (found) C 74.24, H 7.68, N 9.17. 19. (pyEA-AriPr2)2Co(py) (1-Co-py). To a 50 mL flask charged with CoCl2py4 (311 mg, 0.697 mmol) and (pyEA-AriPr2)K (444 mg, 1.39 mmol) was added 25 mL Et2O (25 mL) via vacuum transfer. The mixture was stirred at -78 °C for 2 h, then slowly warmed over 3 hr to 20 °C, and stirred an additional 12 h. Solvent was removed in vacuo to give a red-brown solid, 25 mL pentane was added, and the mixture was filtered. The desired product was extracted from the filter cake by washing until extracts were pale yellow. Solvent was removed to give 2-Co-py as a brick red solid (278 mg, 57 %). 1H NMR (C6D6): δ -113.93 (ν1/2 = 775 Hz), -98.79 (ν1/2 = 841 Hz), -16.20 (ν1/2 = 78 Hz), -7.58 (ν1/2 = 2044 Hz), 14.04 (ν1/2 = 2039 Hz), 43 28.22 (ν1/2 = 122 Hz), 43.02 (ν1/2 = 1160 Hz), 48.91 (ν1/2 = 210 Hz), 66.82 (ν1/2 = 3160 Hz), 96.68 (ν1/2 = 1520 Hz). μeff (Evans) = 3.9(1) μB. Anal. for C43H51CoN5 (calc.) C 74.12, H 7.38, N 10.05; (found) C 73.96, H 7.51, N 9.95. 20. (κ-C,N-pyEA-AriPr2)3Co (2). To a 25 mL flask charged with CoCl2 (51 mg, 0.39 mmol) and (pyEA-AriPr2)K (250 mg, 0.78 mmol) was transferred 10 mL THF via vacuum transfer. The mixture was allowed to warm from -78 °C to 20 °C and stirred for 10 h, resulting in a dark red-brown solution. The solvent was removed and 10 mL pentane (10 mL) was added. The mixture was warmed to 20 °C and filtered. The filter cake was washed with pentane until extracts were colorless. The resulting purple-gray filter cake was extracted with benzene to give a purple solution. Solvent was removed in vacuo to give Co(PyImCH2)3 as a red-purple solid (24 mg, 0.027 mmol, 7 %). Crystals suitable for X-ray diffraction were obtained via slow evaporation of a concentrated benzene solution. 1H NMR (C6D6): δ 0.88 (3H, d, 7 Hz, iPr CH3), 1.00 (3H, d, 7 Hz, iPr CH3), 1.13 (3H, d, 7 Hz, iPr CH3), 1.16 (3H, d, 7 Hz, iPr CH3), 1.67 (1H, d, 14.5 Hz, Co-CHa), 2.27 (1H, d, 14.5 Hz, Co-CHb), 2.36 (1H, sept, 7 Hz, iPr C-H), 2.81 (1H, sept, 7 Hz, iPr C-H), 6.39 (1H, t, 6 Hz, py C-H), 6.99 (1H, t, 8 Hz, py C-H), 7.13 (3H, m, Ph C-H), 7.50 (1H, d, 5 Hz, py C-H), 8.18 (1H, d, 8 Hz, py C-H). 13C NMR (THF-d8): δ 20.16 (Co-C, ν1/2 = 37 Hz), 23.10 (iPr Me) , 23.17 (iPr Me), 23.83 (iPr Me), 23.96 (iPr Me), 28.79 (iPr CH), 29.02 (iPr CH), 122.98 (Ph ipso-C), 123.45 (Ph p-C), 123.49 (Ph m-C), 123.69 (5-py), 126.91 (3-py), 135.73 (Ph o-C), 136.70 (Ph o-C), 136.99 (4-py), 148.58 (6-py), 149.91 (2-py), 182.38 (Imine). Anal. for C57H69CoN6 (calc.) C 76.31, H 7.75, N 9.37; (found) C 76.41, H 7.45, N 9.18. 44 21. {κ-N,N-N(C6H3(2-iPr)CMe2C(Me)(2-py))}2Co (3-Co). A glass bomb was charged with 1-Co-py (105 mg, 0.15 mmol) and benzene (7 mL). The mixture was heated at 140 °C for 36 h, resulting in a color change to dark red. Solvent was removed to give a dark red oil, which was triturated with pentane (2 x 5 mL) to give a dark red solid. 1H NMR showed a mixture of 2 paramagnetic species in 9:1 ratio. 3Co, the major product, was isolated as dark crystals (66 mg, 71%) upon slow evaporation of a concentrated benzene solution. 1H NMR (C6D6): δ -80.49 (ν1/2 = 180 Hz), -21.24 (ν1/2 = 337 Hz), -13.07 (ν1/2 = 156 Hz), 12.52 (ν1/2 = 77 Hz), 28.37 (ν1/2 = 103 Hz), 29.07 (ν1/2 = 1000 Hz), 33.71 (ν1/2 = 54 Hz), 43.78 (ν1/2 = 750 Hz), 48.14 (ν1/2 = 202 Hz), 69.99 (ν1/2 = 174 Hz), 89.68 (ν1/2 = 1178 Hz), 99.27 (ν1/2 = 485 Hz). μeff (Evans) = 4.2(1) μB. Anal. for C38H46CoN4 (calc.) C 73.88, H 7.51, N 9.07; (found) C 73.74, H 7.61, N 9.09. 22. Aqueous quench of 3-Co affords indolamine. X-ray quality crystals of 3-Co (10 mg) were dissolved in C6D6. One drop of water was added and the resultant mixture was filtered through Celite to afford a pale yellow solution. 1H NMR (C6D6): δ 0.79 (3H, s, indoline CH3), 1.20 (3H, d, 7 Hz, iPr CH3), 1.27 (3H, d, 7 Hz, iPr CH3), 1.61 (3H, s, indoline CH3), 1.65 (3H, s, indoline CH3), 2.74 (1H, sept, iPr CH), 3.55 (1H, br s, NH), 6.67 (1H, dd, 7 Hz, 5 Hz, py), 6.93 (2H, m, Ph), 7.06 (1H, m, Ph), 7.10-7.20 (1H, m, py), 7.71 (1H, d, 8 Hz, py), 8.51 (1H, d, 5 Hz). NMR tube or small pot scale reactions. 23. 1-Fe and tBuI. To a J-Young tube charged with 1-Fe (16 mg, 0.026 mmol) in C6D6 (500 μL) was added tertbutyliodide (3.0 μL, 0.025 mmol) via microsyringe, resulting in a color change from red-brown to dark green. After 12 hr at 23 °C, the 1H NMR spectrum showed 45 isobutylene (δ 1.58 (s), 4.74 (s)) in addition to several new paramagnetic products. 24. 1-M to 3-M (M = Cr, Mn, Fe) rearrangements. a. 3-Cr. An NMR tube was charged with 1-Cr (12 mg) and C6H6 (0.50 mL). The tube was sealed and heated at 140 °C for 36 hr. The tube was cracked and 1 drop of water added. The mixture was filtered through Celite. A 5:1 ratio of indoline (see procedure 25): (2,6iPr2C6H3)N=C(Me)(2-py) was observed by 1H NMR spectroscopy. b. 3-Mn. The same procedure of a. was used, with a 4:1 ratio of indoline:(2,6-iPr2C6H3)N=C(Me)(2py) obtained by 1H NMR spectroscopy. c. 3-Fe. The same procedure of a. was used, with a 0.8:1 ratio of indoline:(2,6-iPr2C6H3)N=C(Me)(2-py) obtained by 1H NMR spectroscopy. 25. {κ-N,N-N(C6H3(2-iPr)CMe2C(Me)(2-py))}Li from (pyEA-AriPr2)Li. (pyEA-AriPr2)Li (28 mg) was dissolved in THF-d8, and the orange solution was heated at 140 °C for days, resulting in a darkening of the solution. 1H NMR (thf-d8): δ 0.43 (3H, s), 1.16 (3H, d, 7 Hz, iPr CH3), 1.21 (3H, d, 7 Hz, iPr CH3), 1.25 (3H, s), 1.48 (3H, s), 3.09 (1H, sept, iPr CH), 5.71 (1H, t, 7 Hz, Ph), 6.32 (1H, d, 7.5 Hz, Ph), 6.50 (1H, d, 7.5 Hz, Ph), 7.14 (1H, t, 6 Hz, py), 7.53 (1H, d, 8 Hz, py), 7.68 (1H, t, 7.5 Hz, py), 8.37 (1H, d, 4 Hz, py). 13C NMR (thf-d8): δ 22.41, 22.48, 24.19, 28.13, 28.84. 29.06, 49.43, 81.05, 106.47, 118.95, 121.57, 122.97, 123.36, 125.19, 136.46, 138.38, 147.52, 160.87, 172.99. 26. a. {κ-N,N-N(C6H3(2-Et)CHMeC(Me)(2-py))}Li from (pyEA-ArEt2)Li. (pyEA-ArEt2)Li (30 mg) was dissolved in C6D6 (500 μL) with a drop of thf-d8. The resultant orange solution was heated at 130 °C for 3 days, resulting in a color change to green. 1H NMR (C6D6/THF-d8): δ 0.75 (3H, d. 6.5 Hz), 0.83 (3H, t, 7 Hz), 1.69 46 (1H, m), 1.71 (3H, s), 2.11 (1H, m), 3.07 (1H, q, 7 Hz), 6.33 (1H, t, 6 Hz), 6.65 (1H, t, 7 Hz), 6.95 (1H, d, 8 Hz), 7.07 (1H, t, 8 Hz), 7.11 (1H, t, 8 Hz), 7.20 (1H, d, 7 Hz), 7.79 (1H, d, 5 Hz). 13C{1H} NMR (C6D6/THF-d8, 125 MHz, 295 K): δ 11.78, 20.84, 23.38, 30.97, 51.87, 76.65, 110.79, 120.64, 120.79, 121.70, 122.96, 124.39, 133.94, 136.45, 147.19, 161.31, 169.97. b. Concentration dependence. Experiments were run in parallel at 130 °C, with (pyEA-ArEt2)Li concentrations of 0.056 M (kobs = 7.1(1) x 10-4 s-1), 0.21 M (kobs = 6.7(1) x 10-4 s-1), and 0.31 M (kobs = 6.8(2) x 10-4 s-1). 27. {κ-N,N-N(C6H3(2-Me)CH2C(Me)(2-py))}Li from (pyEA-ArMe2)Li. (pyEA-ArMe2)Li (30 mg) was dissolved in THF-d8 (450 μL). The resultant orange solution was heated at 130 °C for 24 h, resulting in a color change to green. 1H NMR (THF-d8): δ 1.26 (3H, s), 1.98 (3H, s), 3.01 (1H, d, 14 Hz), 3.05 (1H, d, 14 Hz), 5.56 (1H, t, 7 Hz), 6.37 (1H, d, 7 Hz), 6.50 (1H, d, 7 Hz), 7.08 (1H, “t”, 6 Hz), 7.27 (1H, d, 8 Hz), 7.65 (1H, t, 8 Hz), 8.32 (1H, d, 5 Hz). 13C: δ 19.01, 34.53, 46.94, 105.16, 112.96, 121.37, 122.19, 126.11, 128.75, 137.94, 147.88, 163.99, 176.14. 28. {κ-N,N-N(C6H4CH2C(Me)(2-py))}Li from (pyEA-o-tol)Li. (pyEA-otol)Li (25 mg) was dissolved in THF-d8 (450 μL). The orange solution was heated at 130 °C for 48 hr, resulting in a green solution. 1H NMR (THF-d8): δ 1.58 (3H, s), 2.84 (1H, d, 15 Hz), 2.93 (1H, d, 15 Hz), 5.85 (1H, t, 7 Hz), 6.51 (1H, br s), 6.65 (1H, d, 7 Hz), 6.67 (1H, d, 7 Hz), 6.86 (1H, br m), 7.30 (1H, d, 8 Hz), 7.52 (1H, t, 7 Hz), 8.09 (1H, br s). 13C NMR (THF-d8): δ 31.77, 49.45, 74.32, 107.93, 108.70, 121.32, 122.24, 123.60, 128.25, 128.54, 137.50, 148.15, 165.91, 174.71. Kinetics measurements. Kinetics experiments were run in triplicate, and constant temperature conditions were maintained using a Thermo Scientific AC200 47 heated immersion circulator. Reaction progress was monitored by NMR using the integration of the vinyl C-H resonance relative to that of ferrocene as an internal standard. First order rate constants were determined by fitting to an exponential decay function. 29. Conversion of 1-M to 3-M. An NMR tube was charged with 1-M (13 mg, M = Cr, Mn, Fe, Copy), THF-d8 (450 μL), and ferrocene (~ 1 mg, integration standard). The tube was sealed and heated at 130 °C. For 1-Fe, rate constant determination was complicated by severe broadening of the 1H resonances within the first 12 h of reaction time. For 1-Mn, determination of a reliable rate constant was not possible due to unreliable integrations of the very broad 1H resonances. 30. (pyEA-ArMe2)Li cyclization. An NMR tube was charged with (pyEAArMe2)Li (10 mg, 0.043 mmol), THF-d8 (400 μL), and ~1 mg of ferrocene (internal standard). The tube was sealed under vacuum. The sample was heated at regular time intervals and then cooled to 20 °C to collect a 1H NMR spectrum. Reaction progress was followed to 90 % conversion. Kinetics measurements were made at 100, 120, 130, 140, and 150 °C. 31. (pyEA-ArEt2)Li cyclization. An NMR tube was charged with (pyEAArEt2)Li (11 mg, 0.043 mmol), THF-d8 (400 μL), and ~1 mg of ferrocene (internal standard). The cyclization was monitored as in procedure 29, but only at 130 °C. 32. (pyEA-AriPr2)Li cyclization. An NMR tube was charged with (pyEAAriPr2)Li (11 mg, 0.043 mmol), THF-d8 (400 μL), and ~1 mg of ferrocene (internal standard). The cyclization was monitored as in procedure 29, but only at 130 °C. 33. (pyEA-o-tol)Li vs. (2-py)C(=CD2)N(o-CD3-C6H4)Li (KIE(kH/kD5). 48 NMR tubes were charged with each Li compound (10 mg), THF-d8 (450 μL), and ferrocene (~ 1 mg). Triplicate tubes were sealed and heated at 130 °C in tandem to afford kH/kD5. 34. (pyEA-o-tol)Li vs. (pyEA-C6H4-o-CD3)Li (KIE(kH/kD3). NMR tubes were charged with each Li compound (10 mg), THF-d8 (450 μL), and ferrocene (~ 1 mg). Triplicate tubes were sealed and heated at 130 °C in tandem to afford kH/kD3. Deuterium scrambling between o-CD3 and =CH2 positions was noted. 35. EIE Analysis for (pyEA-C6H4-o-CD3)Li. For 1H NMR analysis, an NMR tube was charged with (pyEA-C6H4-o-CD3)Li (10 mg), THF-d8 (450 μL), and ferrocene (~ 1mg). For 2H NMR analysis, an NMR tube was charged with (pyEAC6H4-o-CD3)Li (10 mg) and THF (450 μL).The tubes were heated at 130 °C. Time intervals of 3 min for recording 1H NMR spectra were used until the system reached equilibrium (~ 50 min). At equilibrium, the ratio =C(H/D)2:o-C(H/D)3 was determined to be 0.89:1.11 (equating the integration of the vinyl protons at t = 0 to 2 protons). For the 2H NMR spectroscopic experiment, the tube was heated for 50 min. At equilibrium, the ratio of =C(H/D)2:o-C(H/D)3 was determined to be 1.1:1.9. Single crystal X-ray diffraction studies. Upon isolation, the crystals were covered in polyisobutenes and placed under a 173 K N2 stream on the goniometer head of a Siemens P4 SMART CCD area detector (graphite-monochromated MoKα radiation, λ = 0.71073 Å). The structures were solved by direct methods (SHELXS). All non-hydrogen atoms were refined anisotropically unless stated, and hydrogen atoms were treated as idealized contributions (Riding model). 49 REFERENCES (1) Luca, O. R.; Crabtree, R. H. Chem. Soc. Rev. 2013, 42 (4), 1440–1459. (2) Kaim, W.; Schwederski, B. Coord. Chem. Rev. 2010, 254 (13–14), 1580–1588. (3) Caulton, K. G. Eur. J. Inorg. Chem. 2012, 2012 (3), 435–443. (4) Evangelio, E.; Ruiz-Molina, D. Eur. J. Inorg. Chem. 2005, 2005 (15), 2957– 2971. (5) Ray, K.; Petrenko, T.; Wieghardt, K.; Neese, F. Dalton Trans. 2007, 1552– 1566. (6) Eisenberg, R.; Gray, H. B. Inorg. Chem. 2011, 50 (20), 9741–9751. (7) Pierpont, C. G. Coord. Chem. Rev. 2001, 216–217, 99–125. (8) Pierpont, C. G. Coord. Chem. Rev. 2001, 219–221, 415–433. (9) Ghosh, M.; Sproules, S.; Weyhermüller, T.; Wieghardt, K. Inorg. Chem. 2008, 47 (13), 5963–5970. (10) Khusniyarov, M. M.; Weyhermüller, T.; Bill, E.; Wieghardt, K. J. Am. Chem. Soc. 2009, 131 (3), 1208–1221. (11) Bart, S. C.; Lobkovsky, E.; Chirik, P. J. J. Am. Chem. Soc. 2004, 126 (42), 13794–13807. (12) Bart, S. C.; Chłopek, K.; Bill, E.; Bouwkamp, M. W.; Lobkovsky, E.; Neese, F.; Wieghardt, K.; Chirik, P. J. J. Am. Chem. Soc. 2006, 128 (42), 13901–13912. (13) Russell, S. K.; Darmon, J. M.; Lobkovsky, E.; Chirik, P. J. Inorg. Chem. 2010, 49 (6), 2782–2792. (14) Stieber, S. C. E.; Milsmann, C.; Hoyt, J. M.; Turner, Z. R.; Finkelstein, K. D.; Wieghardt, K.; DeBeer, S.; Chirik, P. J. Inorg. Chem. 2012, 51 (6), 3770–3785. (15) Russell, S. K.; Bowman, A. C.; Lobkovsky, E.; Wieghardt, K.; Chirik, P. J. Eur. J. Inorg. Chem. 2012, 2012 (3), 535–545. (16) Darmon, J. M.; Stieber, S. C. E.; Sylvester, K. T.; Fernández, I.; Lobkovsky, E.; Semproni, S. P.; Bill, E.; Wieghardt, K.; DeBeer, S.; Chirik, P. J. J. Am. Chem. Soc. 2012, 134 (41), 17125–17137. (17) Tondreau, A. M.; Stieber, S. C. E.; Milsmann, C.; Lobkovsky, E.; Weyhermüller, T.; Semproni, S. P.; Chirik, P. J. Inorg. Chem. 2013, 52 (2), 635–646. 50 (18) Russell, S. K.; Hoyt, J. M.; Bart, S. C.; Milsmann, C.; Stieber, S. C. E.; Semproni, S. P.; DeBeer, S.; Chirik, P. J. Chem. Sci. 2014, 5 (3), 1168–1174. (19) Tondreau, A. M.; Milsmann, C.; Patrick, A. D.; Hoyt, H. M.; Lobkovsky, E.; Wieghardt, K.; Chirik, P. J. J. Am. Chem. Soc. 2010, 132 (42), 15046–15059. (20) Russell, S. K.; Lobkovsky, E.; Chirik, P. J. J. Am. Chem. Soc. 2011, 133 (23), 8858–8861. (21) Hojilla Atienza, C. C.; Milsmann, C.; Lobkovsky, E.; Chirik, P. J. Angew. Chem. Int. Ed. 2011, 50 (35), 8143–8147. (22) Monfette, S.; Turner, Z. R.; Semproni, S. P.; Chirik, P. J. J. Am. Chem. Soc. 2012, 134 (10), 4561–4564. (23) Tondreau, A. M.; Atienza, C. C. H.; Weller, K. J.; Nye, S. A.; Lewis, K. M.; Delis, J. G. P.; Chirik, P. J. Science 2012, 335 (6068), 567–570. (24) Tondreau, A. M.; Atienza, C. C. H.; Darmon, J. M.; Milsmann, C.; Hoyt, H. M.; Weller, K. J.; Nye, S. A.; Lewis, K. M.; Boyer, J.; Delis, J. G. P.; Lobkovsky, E.; Chirik, P. J. Organometallics 2012, 31 (13), 4886–4893. (25) Yu, R. P.; Darmon, J. M.; Hoyt, J. M.; Margulieux, G. W.; Turner, Z. R.; Chirik, P. J. ACS Catal. 2012, 2 (8), 1760–1764. (26) Hoyt, J. M.; Sylvester, K. T.; Semproni, S. P.; Chirik, P. J. J. Am. Chem. Soc. 2013, 135 (12), 4862–4877. (27) Semproni, S. P.; Hojilla Atienza, C. C.; Chirik, P. J. Chem. Sci. 2014, 5 (5), 1956–1960. (28) Hojilla Atienza, C. C.; Milsmann, C.; Semproni, S. P.; Turner, Z. R.; Chirik, P. J. Inorg. Chem. 2013, 52 (9), 5403–5417. (29) Budzelaar, P. H. M. Eur. J. Inorg. Chem. 2012, 2012 (3), 530–534. (30) Zhu, D.; Thapa, I.; Korobkov, I.; Gambarotta, S.; Budzelaar, P. H. M. Inorg. Chem. 2011, 50 (20), 9879–9887. (31) Zhu, D.; Budzelaar, P. H. M. Organometallics 2010, 29 (22), 5759–5761. (32) Knijnenburg, Q.; Gambarotta, S.; Budzelaar, P. H. M. Dalton Trans. 2006, No. 46, 5442–5448. (33) Lu, C. C.; Bill, E.; Weyhermüller, T.; Bothe, E.; Wieghardt, K. J. Am. Chem. Soc. 2008, 130 (10), 3181–3197. 51 (34) Lu, C. C.; Weyhermüller, T.; Bill, E.; Wieghardt, K. Inorg. Chem. 2009, 48 (13), 6055–6064. (35) Bheemaraju, A.; Lord, R. L.; Müller, P.; Groysman, S. Organometallics 2012, 31 (6), 2120–2123. (36) Volpe, E. C.; Wolczanski, P. T.; Darmon, J. M.; Lobkovsky, E. B. Polyhedron 2013, 52, 406–415. (37) Williams, V. A.; Hulley, E. B.; Wolczanski, P. T.; Lancaster, K. M.; Lobkovsky, E. B. Chem. Sci. 2013, 4 (9), 3636–3648. (38) Morris, W. D.; Wolczanski, P. T.; Sutter, J.; Meyer, K.; Cundari, T. R.; Lobkovsky, E. B. Inorg. Chem. 2014, 53 (14), 7467–7484. (39) Blackmore, K. J.; Ziller, J. W.; Heyduk, A. F. Inorg. Chem. 2005, 44 (16), 5559–5561. (40) Haneline, M. R.; Heyduk, A. F. J. Am. Chem. Soc. 2006, 128 (26), 8410–8411. (41) Nguyen, A. I.; Zarkesh, R. A.; Lacy, D. C.; Thorson, M. K.; Heyduk, A. F. Chem. Sci. 2011, 2 (1), 166–169. (42) Milsmann, C.; Turner, Z. R.; Semproni, S. P.; Chirik, P. J. Angew. Chem. Int. Ed. 2012, 51 (22), 5386–5390. (43) Klein, H.-F.; Karsch, H. H. Chem. Ber. 1975, 108 (3), 956–966. (44) Ren, X.; Alleyne, B. D.; Djurovich, P. I.; Adachi, C.; Tsyba, I.; Bau, R.; Thompson, M. E. Inorg. Chem. 2004, 43 (5), 1697–1707. (45) Berben, L. A.; Long, J. R. Inorg. Chem. 2005, 44 (23), 8459–8468. (46) Cope, A. C.; Gourley, R. N. J. Organomet. Chem. 1967, 8 (3), 527–533. (47) Drevs, H. Z. Für Anorg. Allg. Chem. 1991, 605 (1), 145–150. (48) Yamada, H.; Matsukawa, S.; Yamamoto, Y. React. Control Dyn. Complexes 2007, 692 (1–3), 271–277. (49) Brian N. Figgis, Michael A. Hitchman. Ligand Field Theory and Its Applications; Wiley-VCH: New York, 2000. (50) Schöffel, J.; Šušnjar, N.; Nückel, S.; Sieh, D.; Burger, P. Eur. J. Inorg. Chem. 2010, 2010 (31), 4911–4915. (51) Eckert, N. A.; Vaddadi, S.; Stoian, S.; Lachicotte, R. J.; Cundari, T. R.; Holland, P. L. Angew. Chem. Int. Ed. 2006, 45 (41), 6868–6871. 52 (52) Jiao, R.; Xue, M.; Shen, X.; Zhang, Y.; Yao, Y.; Shen, Q. Eur. J. Inorg. Chem. 2011, 2011 (9), 1448–1453. (53) Chandrasekhar, S.; Basu, D.; Raji Reddy, C. Synthesis 2007, 2007 (10), 1509– 1512. (54) Rueping, M.; Brinkmann, C.; Antonchick, A. P.; Atodiresei, I. Org. Lett. 2010, 12 (20), 4604–4607. (55) Mei, T.-S.; Wang, X.; Yu, J.-Q. J. Am. Chem. Soc. 2009, 131 (31), 10806– 10807. (56) Zhou, F.; Guo, J.; Liu, J.; Ding, K.; Yu, S.; Cai, Q. J. Am. Chem. Soc. 2012, 134 (35), 14326–14329. 53 Chapter 2. Iron(II) Complexes Bearing ortho-metalated Benzyldialkylphosphine Ligands as Potential Precursors to Iron(IV) Alkylidene Complexes Introduction Olefin metathesis is a process by which the bonds of alkene substrates are purposefully rearranged to generate new alkenes of higher functionality and/or higher synthetic value. The 2005 Nobel Prize in Chemistry was given to Schrock, Grubbs, and Chauvin for their seminal contributions to the field.1–3 Among its applications, olefin metathesis has been utilized for the synthesis of substituted alkenes (via olefin cross metathesis), cyclic alkenes (via ring closing metathesis, RCM), and unsaturated polymers (via ring opening metathesis polymerization, ROMP). The operative catalysts for these transformations are transition metal alkylidene complexes, which contain a metal-carbon double bond. Several notable examples are provided in Figure 2.1. The field of olefin metathesis has largely been dominated by ruthenium,4–7 molybdenum,8,9 and tungsten catalysts, though some recent vanadium alkylidene Figure 2.1. Select examples of olefin metathesis catalysts. 54 complexes10 have shown excellent activity for ROMP catalysis. Given this stark disparity between first row and later row transition metal catalysts, we sought to pursue the synthesis of an iron analog to the well-studied ruthenium catalysts. Scheme 2.1. Representative examples of the synthesis of iron alkylidene complexes. The synthesis and reactivity of iron alkylidene complexes have been investigated by several research groups over the past 50 years. It is somewhat surprising that the scope of previously reported iron alkylidene complexes is predominately limited to cationic cyclopentadienyl iron alkylidenes and neutral iron 55 alkylidenes with dianionic tetradentate ancillary ligands. However, there is a marked variance in the methodologies employed for their synthesis, as shown in Scheme 2.1. Representative examples include silyl-mediated methoxide abstraction (A)11 and acidmediated methanol loss (B)12 of an Fe α-methoxyalkyl complex, methylation of a vinyl Fe complex (C)13, protonation of a vinyl Fe complex (D)14, and treatment of an Fe(II) precursor with diazoalkanes (E)15. Unfortunately, none of these complexes have been shown to catalyze olefin metathesis. Complexes containing porphyrin or other dianionic planar-disposed ligands are likely unreactive toward olefin metathesis due to the absence of a cis coordination site necessary for alkene binding. Several of these Fe alkylidenes have been shown to react with alkenes, but form cyclopropanes instead of undergoing olefin metathesis.11,12,16–23 Notably, the first evidence for an Fe alkylidene was the observation by Pettit and Jolly of methylidene transfer to olefins from a proposed [Cp(CO)2Fe=CH2]+ species generated in situ.16 ` To further explore iron(IV) alkylidene synthesis, we first targeted electron-rich Fe(II) complexes that could give the desired alkylidene complexes upon reaction with diazoalkanes. DFT calculations performed by our computational collaborator, Thomas R. Cundari, supported the stability of iron(IV) alkylidene complexes bearing a tetradentate diaryl bis(chelate) ligand framework, which could be formed from the treatment of an iron(II) precursor with a diazoalkane (Scheme 2.2). Efforts to generate the desired iron precursors were hampered by synthetic difficulties, as pursued previously by Wesley Morris in our group. In order to preserve the strong donor properties of the aryl groups but ease the overall synthetic demands, we turned to 56 benzyldialkylphosphine ligand frameworks as a bidentate alternative. Scheme 2.2. Original proposal for iron alkylidene formation. Results and Discussion 2.1. Synthesis of Benzyldiphenylphosphine and Attempted Metalation We chose cis-Me2Fe(PMe3)4 as our initial iron precursor due to its widely demonstrated penchant for chelate-assisted activation of aryl, vinyl, and alkyl C-H and Si-H bonds via loss of methane.24–32 We posited that treatment of cis-Me2Fe(PMe3)4 with two equivalents of benzyldiphenylphosphine would result in double aryl C-H activation to give a bis(bidentate) analog to the iron(II) starting compound in Scheme 2.2. Benzyldiphenylphosphine was synthesized in 83 % yield by treatment of diphenylphoshine with sodium in THF to generate the phosphide anion in situ, followed by treatment with benzyl bromide (Eq. 2.1). The reaction gave trace quantities of bibenzyl and tetraphenyldiphosphine (< 3 % each), which did not seem to influence subsequent reactivity. These byproducts are likely a consequence of the well-known radical reactivity of phosphide reagents with alkyl and aryl halides. 57 Unfortunately, the reaction of cis-Me2Fe(PMe3)4 with 2 equiv. benzyldiphenylphosphine resulted in a mixture of products. In addition, there was no observable difference between the reaction of cis-Me2Fe(PMe3)4 with one versus two equivalents of phosphine, which implies that a second C-H activation does not occur. Notably, Beck et al. have reported that the reaction of cis-Me2Fe(PMe3)4 with 1 equiv. benzyldiphenylphosphine proceeds in fairly low yield (23 %) to give the Fe(II) methyl compound (Eq. 2.2). Efforts to repeat the literature procedure in order to attempt the step-wise synthesis of the desired bis(ligand) complex proved to be unsuccessful. The failure of the C-H activation approach prompted the synthesis of ortho-lithiated benzyldialkylphoshines in order to test the viability of a salt metathesis route. 2.2. Synthesis of 2-lithio-benzyldialkylphosphines, LiBnR2P (R = Ph, Cy) The most convenient route to aryllithium phosphine ligands is lithium-halogen exchange from the corresponding (2-bromobenzyl)dialkyl phosphines. (2bromobenzyl)diphenylphosphonium bromide (BrBnPh2P·HBr) was synthesized in 55 58 % yield by stirring a solution of diphenylphosphine and 2-bromobenzyl bromide in hexanes for 4 d (Eq. 2.3). Treatment of BrBnPh2P·HBr with NEt3 in THF gave the desired (2-bromobenzyl)diphenylphosphine (BrBnPh2P) in 55 % yield (Eq. 2.4). Similarly, dicyclohexylphosphine was treated with 2-bromobenzyl bromide in hexanes to give (2-bromobenzyl)dicyclohexylphosphonium bromide (BrBnCy2P·HBr) in 89 % yield (Eq. 2.5). BrBnCy2P·HBr was deprotonated with LiHMDS in THF to afford BrBnCy2P as a waxy white solid in 91 % yield (Eq. 2.6). The corresponding (2-lithiobenzyl)dialkylphosphine reagents were synthesized by lithium-halogen exchange. BrBnPh2P was treated with nBuLi in Et2O at room temperature to give the diethyl ether adduct of (2-lithiobenzyl)diphenylphosphine, LiBnPh2P·OEt2, as a pale yellow solid in 82 % yield (Eq. 2.7). Likewise, BrBnCy2P 59 was treated with nBuLi in Et2O to afford LiBnCy2P·OEt2 in 75 % yield as a white solid (Eq. 2.8). 2.3. Metalation Reactions of (2-lithiobenzyl)dialkylphosphines with FeCl2(PMe3)2 FeCl2(PMe3)2 was chosen as the iron precursor with the expectation that the extra PMe3 ligands would provide a stronger ligand field and give rise to low spin Fe(II) complexes. FeCl2(PMe3)2 was treated with 2 equiv. LiBnPh2P·OEt2 in Et2O to give compound 4 as an orange crystalline solid in 81 % yield (Eq. 2.9). Figure 2.2 shows all the possible isomers (with enantiomers omitted) for a complex with the general constitution of Fe(P,C)2(PMe3)2. Notable spectroscopic data include four inequivalent 31P resonances which all couple with each other, as well as four inequivalent benzylic protons by 1H NMR. Structures A and B contain coplanar P,C ligands and would be expected to have a single benzylic proton resonance. Also, structures C and D have a C2 rotation axis and should have only two benzylic resonances. This leaves E as the only structure consistent with the spectroscopic data. 60 Figure 2.2. Possible isomers for compound 4. Note: enantiomers of C, D, and E have been excluded for simplicity. When FeCl2(PMe3)2 was treated with 2 equiv. LiBnCy2P·OEt2 in Et2O, compound 5 was isolated as an oily orange solid (Eq. 2.10). An aqueous quench showed only BnCy2P and PMe3 in a 2:1 ratio, thus strongly suggesting that compound 5 is 5-coordinate, with two P,C bidentate ligands and a sole PMe3. Surprisingly, 5 is paramagnetic, with a solution magnetic moment of 3.0(1) μB, as determined by Evans’ method . Unfortunately, it has not been possible to corroborate the structure of 5 by X-ray crystallography due to its high solubility in all solvents and its oily nature. 61 Figure 2.3. D-orbital splitting diagram of compound 5 in idealized tbp geometry The paramagnetism of compound 5 is interesting. Based on the magnetic moment, compound 5 is an intermediate spin S = 1 complex. The expected structure, based on electronic considerations, has aryls and the lone PMe3 ligand in the equatorial plane and the chelating phosphines in the apical positions. This ligand arrangement minimizes the overall energy of the metal complex by maximizing π backbonding to the phosphines. A crude d-orbital splitting diagram is shown in Figure 2.3. For an idealized trigonal bipyramidal (tbp) geometry, the energy separation between the dxy and the dx2-y2 orbitals may be small enough that the triplet state is 62 lowest in energy. 2.4. Reaction of Compounds 4 and 5 with Diphenyldiazomethane In an effort to generate iron(IV) alkylidene complexes with a diphenylcarbene ligand, compounds 4 and 5 were treated with diphenyldiazomethane, Ph2C=N2. When a solution of 4 in C6D6 was treated with Ph2C=N2 at room temperature, no reaction was observed. Heating the mixture was not pursued due to the known decomposition of Ph2C=N2 to benzophenone azine, Ph2C=N-N=CPh2.33 Similarly, a solution of 5 in C6D6 was treated with Ph2C=N2, resulting in the formation of at least one new paramagnetic product. If the desired alkylidene was formed, it would likely be diamagnetic. Since no new diamagnetic products were formed, and the reaction did not appear to go cleanly, the result was not pursued. One possibility is that a simple adduct of Ph2C=N2 was formed under the reaction conditions (Eq. 2.11). 2.5. Other Metalation Attempts with Fe We next pursued the synthesis of bis(aryl) iron(II) complexes without PMe3, as we hoped that the use of more weakly binding ligands would result in improved reactivity with diazo reagents. FeBr2(THF)2 was treated with 2 equiv. LiBnCy2P·OEt2 in Et2O with and without additional ligands added. When the reaction was conducted 63 without added ligands or with diphenylacetylene, 2,2’-bipyridine, triphenylphosphine, or ethylene, an intractable mixture was obtained (Scheme 2.3). With the exception of the 2,2’-bipyridine reaction, which gave a purple solid, a brown oily residue was invariably formed. Scheme 2.3. Reaction of FeBr2(THF)2 with LiBnCy2P·OEt2 in the presence of various ligands. In one last attempt, FeCl2(py)4 was treated with 2 equiv. LiBnCy2P·OEt2 in THF to give a purple residue. Dissolution of the solid in benzene afforded a red solution from which a light red diamagnetic compound was obtained. Unfortunately, the compound persisted upon the addition of water. The tentative assignment is that this isolated product is a biaryl compound formed via aryl-aryl coupling (Eq. 2.11). This compound could form by metalation of two ligand equivalents followed by reductive elimination or via reduction of the iron precursor by LiBnCy2P·OEt2, followed by radical C-C coupling. 64 Conclusions While attempts to generate cyclometalated benzyldiphenylphosphine iron complexes via cis-Me2Fe(PMe3)4-mediated C-H activation were unsuccessful, a salt metathesis route in which FeCl2(PMe3)2 was treated with 2 equiv. LiBnR2P·OEt2 (R = Ph, Cy) was successfully employed to generate compounds 4 and 5 in high yields. While 4 is a diamagnetic bis(trimethylphosphine) iron complex, 5 is an intermediate S = 1 mono(trimethylphosphine) iron complex. Unfortunately, no formation of iron(IV) alkylidene complexes was observed upon treating 4 and 5 with diphenyldiazomethane. Additional efforts to synthesize iron(II) complexes without trimethylphosphine ligands gave intractable mixtures of products or undesirable biaryl formation via C-C coupling. 65 Experimental General Considerations. All manipulations were performed using either glovebox or high vacuum line techniques. All glassware was oven dried. THF and ether were distilled under nitrogen from purple sodium benzophenone ketyl and vacuum transferred from the same prior to use. Hydrocarbon solvents were treated in the same manner with the addition of 1-2 mL/L tetraglyme. Benzene-d6 and was dried over sodium, vacuum transferred and stored over sodium. THF-d8 was dried over sodium and vacuum transferred from sodium benzophenone ketyl prior to use. Lithium bis(trimethylsilyl)amide was purchased from Aldrich and recrystallized from hexanes prior to use. All other chemicals were commercially available and used as received. NMR spectra were obtained using an INOVA 400 MHz and 500 MHz spectrometers. Chemical shifts are reported relative to benzene-d6 (1H δ 7.16; 13C{1H} δ 128.39) and THF-d8 (1H δ 3.58; 13C{1H} δ 67.57). Multidimensional techniques were conducted using INOVA software affiliated with the spectrometers. Magnetic measurements obtained in solution were conducted via Evans' method in benzene-d6. Procedures. 1. Benzyldiphenylphosphine, BnPh2P. A 100 mL flask was charged with Na0 (126 mg, 5.48 mmol). 25 mL of THF was transferred to the flask in vacuo. Diphenylphosphine (943 mg, 5.06 mmol) was added dropwise to the flask under Ar, resulting in bubbling and a color change to orange. Stirring was continued under Ar for 26 h. A solution of benzyl bromide (0.60 mL, 5.04 mmol) in THF (6 mL) was added dropwise to the reaction mixture, resulting in a cloudy colorless mixture. 66 Stirring was continued for 12 h to give a yellow solution, which afforded a yellow solid after removal of solvent in vacuo. 30 mL of hexanes was added to the flask and the resultant mixture was filtered. The filtrate was stripped to a yellow solid (988 mg, 83 % yield). 1H NMR (C6D6): δ 2.74 (s, Ph-CH2CH2-Ph), 3.24 (s, 2H, Bn CH2), 6.947.00 (m, 1H, Ph C-H), 7.02-7.07 (m, 10H, Ph C-H), 7.30-7.40 ppm (m, 4H, Ph C-H). 31P NMR (C6D6): δ -15.02 (s, Ph2P-PPh2), -10.22 ppm (s, BnPh2P). 2. (2-bromobenzyl)diphenylphosphonium bromide, BrBnPh2P·HBr. A 250 mL flask was charged with 2-bromobenzyl bromide (9.216 g, 36.9 mmol). 100 mL of hexanes was transferred to the flask to give a colorless solution. Under Ar counter-flow, diphenylphosphine (6.891 g, 37.01 mmol) was added via syringe. The mixture was stirred for 4 d to afford a yellow solution with white precipitate. The mixture was cooled to -78 °C filtered, and washed to afford a white solid (8.757 g, 54.5 % yield). 3. (2-bromobenzyl)diphenylphosphine, BrBnPh2P. A 100 mL flask was charged with BrBnPh2P·HBr (2.562 g, 5.87 mmol). THF (40 mL) and NEt3 (4.0 mL, 28.7 mmol) were transferred to the flask. The resultant mixture was stirred at room temperature for 12 hr, then filtered to remove [HNEt3]Br. The solvent was removed to give the product as a white solid (1.138 g, 54.6 % yield). 1H NMR (C6D6): δ 3.51 (s, 2H, BrBn CH2), 6.58 (t, 1H, 7 Hz, BrBn CH), 6.70 (t, 1H, 7 Hz, BrBn CH), 6.74 (d, 1H, 7 Hz, BrBn CH), 7.05 (br s, 6H, Ph CH), 7.38 ppm (br m, 5H, Ph CH, BrBn CH). 31P NMR (C6D6): δ -12.80 ppm (s). 4. (2-bromobenzyl)dicyclohexylphosphonium bromide, BrBnCy2P·HBr. A 100 mL flask was charged with 2-bromobenzyl bromide (3.78 g, 15.1 mmol). Pentane 67 (25 mL) was transferred to the flask to give a colorless solution. Under a counter-flow of Ar, a solution of dicyclohexylphosphine (3.00 g, 15.1 mmol) in pentane (7 mL) was added via syringe, resulting in a cloudy mixture. The mixture was stirred for 6 d, then solvent was removed in vacuo. 30 mL pentane was transferred to the flask and the mixture was filtered and washed with pentane (4x) to afford a white powder (6.055 g, 89.4 % yield). 5. (2-bromobenzyl)dicyclohexylphosphine, BrBnCy2P. A 50 mL flask was charged with BrBnCy2P·HBr (2.605 g, 5.81 mmol) and LiHMDS (0.956 g, 5.71 mmol). THF (30 mL) was transferred to the flask, affording a yellow solution. After stirring for 16 hr, the volatiles were removed in vacuo to give a yellow oil with white solid. The residue was triturated once with pentane (25 mL). Pentane (15 mL) was transferred to give a white suspension. The mixture was filtered and washed with pentane (4x) to give a colorless filtrate with a white filter cake. The filtrate was stripped to a white solid (1.905 g, 90.9 % yield). 1H NMR (C6D6): δ 1.04-1.36 (m, 10H, Cy), 1.48-1.90 (m, 12 H, Cy), 2.94 (s, 2H, CH2), 6.65 (t, 1H, 8 Hz, BrBn CH), 6.94 (t, 1H, 8 Hz, BrBn CH), 7.41 (d, 1H, 8 Hz, BrBn CH), 7.45 ppm (dt, 1H, 8 Hz, 2 Hz, BrBn CH). 31P NMR (C6D6): δ 2.73 ppm. 6. (2-lithiobenzyl)diphenylphosphine etherate, LiBnPh2P·Et2O0.72. A 50 mL flask was charged with BrBnPh2P (1.143 g, 3.22 mmol). Et2O (20 mL) was transferred to the flask in vacuo. Under Ar counter-flow, nBuLi (1.6 M in hexanes, 2.0 mL, 3.2 mmol) was added dropwise, resulting in a yellow solution with a tan precipitate. The mixture was stirred for 2 hr at 23 °C, filtered, stripped, and the filter cake washed with pentane (2 x 10 mL) to give the product as a white solid (0.864 g, 68 80.5 % yield). 1H NMR (C6D6/THF-d8): δ 1.05 (t, 4.1H, 7 Hz, Et2O), 3.21 (q, 2.9H, 7 Hz, Et2O), 3.80 (s, 2H, LiBn CH2), 7.00 (m, 6H, Ph CH), 7.19 (m, 3H, LiBn CH), 7.48 (m, 4H, Ph CH), 8.47 ppm (br s, 1H, LiBn CH). 31P NMR (C6D6/THF-d8): δ -11.49 ppm (s). 7. (2-lithiobenzyl)dicyclohexylphosphine etherate, LiBnCy2P·Et2O0.80. A 50 mL flask was charged with BrBnCy2P (963 mg, 2.62 mmol). Et2O (15 mL) was transferred to the flask in vacuo, affording a colorless solution. Under an Ar atmosphere at 23 °C, nBuLi (1.6 mL, 1.6 M in hexanes, 2.6 mmol) was added dropwise via syringe, resulting in a yellow solution with white solid. The mixture was stirred for 2 h at 23 °C, then cooled to -30 °C and filtered to collect a pure white solid (715 mg, 77.7 %). 1H NMR (C6D6/THF-d8): δ 1.10 (t, 7 Hz, Et2O), 1.14-1.55 (m, 10H, Cy), 1.55-2.07 (m, 12H, Cy), 3.25 (m, LiBn CH2, Et2O), 7.25 (br s, 1H, LiBn CH), 7.28 (br s, 2H, LiBn CH), 8.44 ppm (br s, 1H, LiBn CH). 31P NMR (C6D6/THF-d8): δ 0.71 ppm (s). 8. (o-C6H4CH2PPh2)2Fe(PMe3)2, 4. A 50 mL flask was charged with FeCl2(PMe3)2 (77 mg, 0.28 mmol) and LiBnPh2P·Et2O0.72 (185 mg, 0.552 mmol). Et2O (10 mL) was transferred to the flask in vacuo. The resultant mixture was stirred at -78 °C for 3 h, then allowed to slowly warm to 23 °C and stirred for 12 h. The resultant orange solution with white solid was stripped to an orange solid. Benzene (10 mL) was transferred to the flask and the resultant mixture filtered to remove LiCl. The solvent was removed to give an orange crystalline solid (127 mg, 62 % yield). 1H NMR (C6D6): δ 0.89 (d, 9H, 7 Hz, PMe3), 1.00 (d, 9H, 6 Hz, PMe3), 2.49 (dd, 1H, 13 Hz, 2J1H-31P = 4 Hz, Bn CH), 2.85 (d, 1H, 13 Hz, Bn CH), 3.81 (dd, 1H, 17 Hz, 2J1H-31P 69 = 4.5 Hz, Bn CH), 4.14 (dd, 1H, 17 Hz, 2J1H-31P = 12 Hz, Bn CH), 5.97 (t, 1H, 8 Hz, Ph CH), 6.65 (m, 2H, Ph CH), 6.86 (m, 6H, Ph CH), 6.98 (m, 6H, Ph CH), 7.11 (m, 3H, Ph CH), 7.42 (t, 2H, 8 Hz, Ph CH), 7.45 (m, 1H, Ph CH), 7.56 (m, 2H, Ph CH), 7.73 (m, 2H, Ph CH). 31P NMR (C6D6): δ -10.46 (ddd, 87 Hz, 35 Hz, 28 Hz), 8.65 (ddd, 33 Hz, 28 Hz, 22 Hz), 20.31 (ddd, 87 Hz, 33 Hz, 22 Hz), 67.67 ppm (dt, 35 Hz, 22 Hz). 9. (o-C6H4CH2PCy2)2Fe(PMe3)2, 5. A flask was charged with FeCl2(PMe3)2 (150 mg, 0.538 mmol) and LiBnCy2P·Et2O0.80 (381 mg, 1.08 mmol). Et2O (15 mL) was transferred to the flask in vacuo. The mixture was slowly allowed to warm to 23 °C and stirred for 14 h to give an orange solution with orange solid. The mixture was filtered and washed until the filter cake was white. The filtrate was stripped to afford an oily orange solid (189 mg, 49.7 % yield). 1H NMR (C6D6): δ -48.46 (ν1/2 = 774 Hz), -25.87 (ν1/2 = 250 Hz), -11.45 (ν1/2 = 495 Hz), -9.06 (ν1/2 = 538 Hz), -5.61 (ν1/2 = 1044 Hz), -2.67 (ν1/2 = 215 Hz), -1.09 (ν1/2 = 122 Hz), 24.63 (ν1/2 = 300 Hz), 27.85 (ν1/2 = 437 Hz), 31.92 ppm (ν1/2 = 733 Hz). 31P NMR (C6D6): δ 15.96 (1P, dd, 128 Hz, 22 Hz), 68.63 (1P, “t”, 23.5 Hz), 70.52 ppm (1P, dd, 128 Hz, 26 Hz). μeff (Evans) = 3.0(1) μB. 70 REFERENCES (1) Schrock, R. R. Angew. Chem. Int. Ed. 2006, 45 (23), 3748–3759. (2) Grubbs, R. H. Angew. Chem. Int. Ed. 2006, 45 (23), 3760–3765. (3) Chauvin, Y. Angew. Chem. Int. Ed. 2006, 45 (23), 3740–3747. (4) Nguyen, S. T.; Johnson, L. K.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1992, 114 (10), 3974–3975. (5) Schwab, P.; France, M. B.; Ziller, J. W.; Grubbs, R. H. Angew. Chem. Int. Ed. Engl. 1995, 34 (18), 2039–2041. (6) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1 (6), 953–956. (7) Kingsbury, J. S.; Harrity, J. P. A.; Bonitatebus, P. J.; Hoveyda, A. H. J. Am. Chem. Soc. 1999, 121 (4), 791–799. (8) Schrock, R. R.; Murdzek, J. S.; Bazan, G. C.; Robbins, J.; DiMare, M.; O’Regan, M. J. Am. Chem. Soc. 1990, 112 (10), 3875–3886. (9) Schrock, R. R.; Hoveyda, A. H. Angew. Chem. Int. Ed. 2003, 42 (38), 4592– 4633. (10) Hou, X.; Nomura, K. J. Am. Chem. Soc. 2015, 137 (14), 4662–4665. (11) Brookhart, M.; Studabaker, W. B.; Husk, G. R. Organometallics 1985, 4 (5), 943–944. (12) Brookhart, M.; Tucker, J. R.; Husk, G. R. J. Am. Chem. Soc. 1981, 103 (4), 979–981. (13) Davison, A.; Selegue, J. P. J. Am. Chem. Soc. 1980, 102 (7), 2455–2456. (14) Kuo, G. H.; Helquist, P.; Kerber, R. C. Organometallics 1984, 3 (5), 806–808. (15) Klose, A.; Hesschenbrouck, J.; Solari, E.; Latronico, M.; Floriani, C.; Re, N.; Chiesi-Villa, A.; Rizzoli, C. J. Organomet. Chem. 1999, 591 (1–2), 45–62. (16) Jolly, P. W.; Pettit, R. J. Am. Chem. Soc. 1966, 88 (21), 5044–5045. (17) Brookhart, M.; Humphrey, M. B.; Kratzer, H. J.; Nelson, G. O. J. Am. Chem. Soc. 1980, 102 (26), 7802–7803. (18) Casey, C. P.; Miles, W. H. Organometallics 1984, 3 (5), 808–809. (19) Brookhart, M.; C.Buck, R. J. Organomet. Chem. 1989, 370 (1–3), 111–127. 71 (20) Wolf, J. R.; Hamaker, C. G.; Djukic, J.-P.; Kodadek, T.; Woo, L. K. J. Am. Chem. Soc. 1995, 117 (36), 9194–9199. (21) Ziegler, C. J.; Suslick, K. S. J. Organomet. Chem. 1997, 528 (1–2), 83–90. (22) Hamaker, C. G.; Mirafzal, G. A.; Woo, L. K. Organometallics 2001, 20 (24), 5171–5176. (23) Li, Y.; Huang, J.-S.; Zhou, Z.-Y.; Che, C.-M.; You, X.-Z. J. Am. Chem. Soc. 2002, 124 (44), 13185–13193. (24) Klein, H.-F.; Camadanli, S.; Beck, R.; Florke, U. Chem. Commun. 2005, No. 3, 381–382. (25) Klein, H.-F.; Camadanli, S.; Beck, R.; Leukel, D.; Flörke, U. Angew. Chem. Int. Ed. 2005, 44 (6), 975–977. (26) Beck, R.; Zheng, T.; Sun, H.; Li, X.; Flörke, U.; Klein, H.-F. J. Organomet. Chem. 2008, 693 (23), 3471–3478. (27) Beck, R.; Sun, H.; Li, X.; Camadanli, S.; Klein, H.-F. Eur. J. Inorg. Chem. 2008, 2008 (21), 3253–3257. (28) Camadanli, S.; Beck, R.; Flörke, U.; Klein, H.-F. Organometallics 2009, 28 (7), 2300–2310. (29) Liu, N.; Li, X.; Sun, H. J. Organomet. Chem. 2011, 696 (13), 2537–2542. (30) Wu, S.; Li, X.; Xiong, Z.; Xu, W.; Lu, Y.; Sun, H. Organometallics 2013, 32 (11), 3227–3237. (31) Xu, G.; Sun, H.; Li, X. Organometallics 2009, 28 (20), 6090–6095. (32) Zhao, H.; Sun, H.; Li, X. Organometallics 2014, 33 (13), 3535–3539. (33) Morris, W. D.; Wolczanski, P. T.; Sutter, J.; Meyer, K.; Cundari, T. R.; Lobkovsky, E. B. Inorg. Chem. 2014, 53 (14), 7467–7484. 72 Chapter 3 Protonation of Fe(II) Vinyl Complexes as a Convenient Entry into Cationic and Neutral Fe(IV) Alkylidene Complexes Introduction In a continuation of our efforts to generate Fe(IV) alkylidene complexes aimed at the expansion of first-row transition metal olefin metathesis catalysis, we next focused our attention on a synthetic scheme involving protonation of iron(II) vinyl complexes (Scheme 3.1), in accordance with literature precedent. Scheme 3.1. Proposed protonation strategy for the synthesis of Fe(IV) alkylidenes. Results and Discussion 3.1. Synthesis and Metalation of 1,2-(E-2-(pyridine-2-yl)vinyl)benzene cis-Me2Fe(PMe3)4 was chosen as a logical iron precursor for the synthesis of iron(II) vinyl complexes. The scope of substrates that can be successfully metalated with cis-Me2Fe(PMe3)4 is generally limited to compounds which bear a donor functionality (e.g. imine, phosphine, thiol) proximate to the C-H bond that is to be activated.1–12 Therefore, target compounds contained either an imine or a pyridine 73 moiety with a pendant alkene or alkyne to serve as the critical site of Fe-C(vinyl) bond formation. Horner-Wadsworth-Emmons olefination was targeted as a convenient route for the synthesis of alkene-containing substrates. To generate a pyridine-containing phosphonium ylide precursor, 2-(chloromethyl)pyridine hydrochloride was treated with NaOH to generate 2-(chloromethyl)pyridine in 88 % yield as a pale yellow liquid (Eq. 3.1). Due to facile decomposition, this reagent had to be used shortly after isolation. A solution of diethylphosphite in benzene was treated with Na0 and heated at reflux for 2 h to generate sodium diethyl phosphite in situ. This solution was then allowed to react with freshly distilled 2-(chloromethyl)pyridine to give (2picolyl)diethylphosphonate in 71 % yield (Eq. 3.2). With the reagent in hand, we pursued the double olefination of ophthalaldehyde to arrive at a tetradentate bis(alkene) ligand with two pyridine donors. (2-picolyl)diethylphosphonate was first treated with LiHMDS in Et2O to prepare the 74 ylide. This solution was then treated with 0.5 equiv o-phthalaldehyde to afford 1,2-(E2-(pyridine-2-yl)vinyl)benzene, (bdvp)H2, in 37 % yield as a white solid (Eq. 3.3). The metalation of (dbvp)H2 with FeMe2(PMe3)4 was conducted in toluene at 20 °C to afford a dark purple solid. NMR spectroscopy showed the presence of 2 products in a 9:1 ratio (Eq. 3.4). The major species is the desired double vinyl C-H activation product (dbvp)Fe (6-PMe3) as determined by NMR and X-ray crystallography. The spectroscopic data of the minor product indicate single vinyl CH bond activation with subsequent insertion of the other alkene into the remaining FeCH3 bond. Spectroscopic evidence includes a pair of doublets in the 31P NMR (2JPP = 24 Hz), as well as additional aliphatic 1H resonances that were not observed for 6PMe3. The low coupling constant is most consistent with a cis orientation of the PMe3 ligands. Efforts towards the isolation of pure 6-PMe3 by changing the solvent and reaction temperature were ultimately unsuccessful. However, the purity proved to be sufficient for subsequent reactivity. 3.2. Protonation of 6-PMe3 Ala’aeddeen Swidan, a former colleague, reported that the protonation of 6- PMe3 with Brookhart’s acid, [H(OEt2)2][BArF4] (ArF = 3,5-(CF3)C6H3),13 resulted in a color change from purple to red. A combined NMR spectroscopic and single crystal 75 X-Ray diffraction study identified the product as the desired Fe(IV) alkylidene complex, 8-PMe3 (Eq. 3.5). Noteworthy features include a 13C NMR chemical shift of 350.6 ppm for the alkylidene carbon as well as an Fe=C bond length of 1.809(4) Å, as compared with the Fe-Cvinyl bond lengths of 1.858(4) Å in 8-PMe3 and 1.888(3) and 1.877(3) Å in 6-PMe3. Unfortunately, 8-PMe3 exhibited no reactivity with olefins at room temperature, with degradation of 8-PMe3 evident at elevated temperatures and under ultraviolet radiation conditions. The lack of reactivity with olefins is likely due to the strong binding of phosphine ligands to the highly Lewis acidic cationic Fe(IV) center. Attempts to synthesize analogous complexes with bulkier, more weakly donating phosphine ligands were only successful for PMe2Ph, though no difference in reactivity with olefins was observed. We next sought to change the geometric constraints of the ligand by synthesizing tridentate ligand frameworks. 3.3. Synthesis and Metalation of N-benzylidene-2-propynylaniline, (pipa)H In order to generate suitable tridentate ligands for the synthesis of iron(II) vinyl complexes, we focused on substrates containing benzaldehyde imine moieties based on extensive prior C-H activation studies with this substrate class by us and others. 76 First, we targeted N-benzylidene-2-propynylaniline,(pipa)H, as a suitable candidate. (pipa)H was synthesized in 83 % yield by condensation of 2-(2-propynyl)aniline and benzaldehyde in CH2Cl2 with 4 Å molecular sieves as the drying agent (Eq. 3.6). As anticipated, treatment of (pipa)H with cis-Me2Fe(PMe3)4 in benzene under a N2 atmosphere resulted in ortho-activation of the benzaldehyde imine moiety and insertion of the alkyne into the remaining Fe-Me bond to form an vinyl iron fragment (Eq. 3.7). Concomitant loss of 2 equiv of PMe3 and 1 equiv of CH4 as byproducts afforded (phimv)Fe-N2, 7, as a dark green crystalline solid in 81 % yield. Based on NMR and IR spectroscopy, the tridentate vinyl-aryl-imine ligand adopts a planar configuration, with two PMe3 ligands cis to the imine and a dinitrogen molecule bound trans to the imine. This assignment is supported by an intense N-N stretch in the IR at 2046 cm-1 and a singlet at 20.56 ppm in the 31P NMR, as well as successful elemental microanalysis. The formation of the dinitrogen complex, (CNC)Fe(PMe3)2N2, instead of the tris(trimethylphosphine) complex, 77 (CNC)Fe(PMe3)3, is likely due to the modest steric interaction between the vinyl methyl and the PMe3 in the hypothetical (CNC)Fe(PMe3)3, as is consistent with previous findings by our group.12 3.4. Protonation of 7 with [H(OEt2)2]BArF4 and Resulting Crystal Structure Compound 7 was treated with [H(OEt2)2]BArF4 (ArF = 3,5-(CF3)2C6H3) in Et2O to give the desired Fe(IV) alkylidene complex, (phimalk)Fe(PMe3)3, 9, as a red solid. Compound 9 has three PMe3 ligands, compared to two for compound 7. The source of the additional PMe3 ligand is likely compound 7, meaning that the reaction proceeds with some decomposition. This problem can be circumvented through addition of 1 equiv of PMe3 to the reaction mixture, thus resulting in an 82 % yield of 9 (Eq. 3.8). The significantly downfield-shifted 13C resonance of the alkylidene carbon (δ = 348.4 ppm) is similar to 8-PMe3. This is well within the range of previously reported Fe carbene 13C chemical shifts, as shown in Table 3.1.14–17 X-ray quality crystals of 9 were grown by slow evaporation of an Et2O/hexanes solution. The crystal structure of 9, along with select bond distances and angles, are shown in Figure 3.1. Table 3.2 shows select crystallographic and refinement data. Compound 9 suffers from disorder in all the PMe3 ligands as well as 78 six of the CF3 groups. The geometry about Fe is pseudo-octahedral, with a Caryl-FeCalkylidene bond angle of 163.36(15) °. The alkylidene Fe-C bond length of 1.899(3) Å is consistent with an iron-carbon double bond. However, it is noticeably longer than that of several other representative diamagnetic Fe alkylidene complexes, including 8PMe3 (Table 1). The strong trans influence imparted by the aryl group in 9, coupled with the more flexible ligand constraints, is likely the cause of this bond elongation. Table 3.1. Alkylidene Fe=C bond lengths and 13C NMR shifts of select Fe=C complexes. Complex (tmtaa)Fe=CPh2 a (TPFPP)Fe=CPh2 b [Cp*(dppe)Fe=CH(Me)]PF6 c 8-PMe3 d (TPFPP)Fe(=CPh2)(MeIm) b 9d d(Fe=C), Å 1.794(3) 1.757(3) 1.787(8) 1.809(4) 1.827(5) 1.899(3) δ (13C=Fe), ppm 313.2 359.0 336.6 350.6 385.4 348.4 [Cp(CO)2Fe=CH(p-OMePh)]OTf f - 310.0 10-Me d - 313.8 11-CH2PMe2 d - 305.8 a Ref. 5 b Ref. 6 c Ref. 7 d This work e Ref. 8 f Note: dppe = bis(diphenylphosphino)ethane; MeIm = 1-methylimidazole 79 Figure 3.1. X-Ray Crystal Structure of 9. Hydrogens, BArF4, and phosphine methyls omitted for clarity. Interatomic distances (Å) and angles (°): Fe-C1, 1.899(3); Fe-N1, 1.933(3); Fe-C17, 2.059(3); Fe-P1, 2.317(2); Fe-P2, 2.226(3); Fe-P3, 2.367(3); C1C2, 1.525(5); N1-Fe-C17, 80.04(14); C1-Fe-C17, 163.36(15); C17-Fe-P1, 92.03(12); C17-Fe-P2, 88.28(13); C17-Fe-P3, 87.16(12); N1-Fe-C1, 83.34(14); N1-Fe-P1, 167.04(14); N1-Fe-P2, 96.52(16); N1-Fe-P3, 79.34(14); C1-Fe-P1, 104.46(12); C1Fe-P2, 92.87(12); C1-Fe-P3, 90.53(13); P1-Fe-P2, 93.45(14); P1-Fe-P3, 90.11(13); P2-Fe-P3, 174.32(13). Table 3.2. Select Crystallographic and Refinement Data for 9. formula formula wt C58H55BF24FeNP3 1381.60 temp, K λ (Å) space group P21/c Reflections Collected Z4 Independent a, Å 18.4232(6) Reflections b, Å c, Å α, deg β, deg γ, deg V, Å3 ρcalc, g·cm-3 μ, mm-1 13.0619(4) 25.9802(8) 90 99.5300(10) 90 6165.6(3) 1.488 0.434 R(int) R indices [I > 2σ(l)]a,b R indices (all data)a,b GOFc Crystal size (mm3) 233(2) 0.71073 35706 9178 0.0393 R1 = 0.0476 wR2 = 0.1109 R1 = 0.0780 wR2 = 0.1273 1.050 0.45 × 0.35 × 0.05 aR1 =ΣFo| - |Fc||/Σ|Fo|. bwR2 = [Σw(|Fo| - |Fc|)2/ΣwFo2]1/2. cGOF (all data) = [Σw(|Fo| |Fc|)2/(n - p)]1/2, n = number of independent reflections, p = number of parameters. 80 3.5. Reactivity of 9 with alkenes With compound 9 in hand, its reactivity with different alkenes was tested (Scheme 3.2). cis-2-pentene was chosen as the first olefin to determine whether 9 would catalyze its cross metathesis to 2-butene and 3-hexene. Unfortunately, when 9 was treated with an excess of cis-2-pentene, no reaction was observed at room temperature. Gradual heating to 80 °C resulted in a color change from red to brown, with iron decomposition evident by disappearance of 1H and 31P NMR resonances corresponding to 9. In addition, no conversion of the alkene to new products was observed. Irradiation of 9 with UV light in the presence of excess cis-2-pentene likewise resulted in the decomposition of 9 and no new organic products. Lastly, 9 was synthesized from 7 and [H(OEt2)2]BArF4 in the presence of cis-2-pentene, but an analysis of the volatiles showed no butene or hexene products. Scheme 3.2. Reactivity of 9 with select alkenes Other alkenes proved to be similarly inert towards reaction with 9. Norbornene showed no reaction at room temperature or 80 °C, at which temperature 81 Fe decomposition was observed. Experiments with UV irradiation yielded identical results. Ethyl vinyl ether also showed no reactivity with compound 9. This general lack of alkene reactivity can be ascribed to the strong binding of the strong phosphine donors to a highly electrophilic metal center. 3.6. Reaction of 9 with MeLi In order to address recalcitrant phosphine dissociation, we sought a route to neutral or even anionic Fe(IV) alkylidene complexes. As the electrophilicity of Fe is systematically decreased, the strength of phosphine binding should similarly decrease, perhaps increasing phosphine lability. The first means to address this was to convert one of the complex’s neutral ligands to an anionic ligand, thus making a neutral metal complex. Fortuitously, the imine functionality in 9 is primed for attack by anionic nucleophiles, thus furnishing an anionic amide ligand. Scheme 3.3. Competing Reaction Pathways of 9 with anionic nucleophiles. 82 However, there are competing pathways that can be operative for these anionic reagents. First, these reagents are often strong bases, meaning that deprotonation of the isopropyl C-H to regenerate 7 is another viable, albeit counter-productive reaction pathway (Scheme 3.3). In addition, attack of the nucleophile at the alkylidene carbon would generate an Fe(II) complex with a tertiary alkyl group, which has potential decomposition pathways, including β-hydride elimination. Since the imine is the least sterically hindered site, we hoped that the desired reaction would be preferred. Alkali metal alkyl reagents were chosen as nucleophiles on account of the large number of commercially available or readily synthesized examples. First, compound 9 was treated with MeLi in Et2O at -78 °C to give 10-Me-N2 in 72 % yield as an oily red-brown solid (Eq. 3.9). The product has an alkylidene 13C NMR resonance at 313.77 ppm, which is shifted upfield by ~ 30 ppm relative to 9. Other notable spectroscopic data include an intense IR stretch at 2058 cm-1 and two doublets in the 31P spectrum at 12.98 and 15.05 ppm with a large coupling constant of 125 Hz. Figure 3.2. Important orbital interaction resulting in favorable N2 binding. 83 These data indicate that the PMe3 ligand trans to the imine in 9 has been displaced by N2, leaving behind the two PMe3 ligands cis to the imine. The binding of N2 in 10-Me-N2 is likely due to the conversion of the imine, a σ donor, to an amide, a π-donor, whose π* combination with the Fe dxz orbital enhances π backbonding into the π-accepting N2 ligand (Figure 3.2). In addition, the CNC bite angle of the tridentate ligand framework can be expected to be less than 180 degrees, based on the crystal structure of compound 7. Therefore, both the alkylidene and the aryl groups will contribute σ* character to the Fe dxy orbital. In analogy to the amide-Fe(dxz) interaction, this will result in enhanced backbonding into the N2 fragment.12 3.7. Reactivity of 10-Me-N2 with Alkenes. In order to compare the alkene reactivity of cationic compound 9 to the neutral 10-Me-N2, 10-Me-N2 was independently treated with an excess of styrene and vinyl ethyl ether in C6D6. No reaction was observed for either under ambient conditions. Unfortunately, heating the reaction mixtures to 80 °C resulted in decomposition of the metal complex, with no new organic products observed by 1H, in analogy to the reactivity of 9 with alkenes (Eq. 3.10). It appears that the phosphine lability of 10Me-N2 is not improved relative to 9, despite the promising observation of substitution of one of the PMe3 ligands with N2. 84 3.8. Reaction of 9 with Benzyl Potassium Compound 9 was treated with benzyl potassium in Et2O to afford a red-purple solid (Scheme 3.4). Dissolution of the solid in C6D6 under a N2 atmosphere resulted in an immediate color change to red-orange. 1H and 31P NMR spectra strongly support the assignment of 10-Bn-N2, with a structure analogous to 10-Me-N2. The 13C NMR resonance of the Fe=C appears at 315.5 ppm, the two 31P resonances appear as doublets (2JPP = 127 Hz) at 12.72 and 15.08 ppm, and there is a strong N≡N IR stretching vibration at 2058 cm-1. Scheme 3.4. Reaction pathway for the formation of 10-Bn-N2. In order to determine the identity of the initially isolated red-purple solid, the same procedure was followed except C6D6 was transferred in vacuo to the flask 85 containing the solid. The resultant solution was added to a J Young tube under Ar to avoid contamination by N2. Notably, there are three doublets of doublets in the 31P NMR with coupling constants of 53, 70, and 92 Hz, consistent with a tris(trimethylphosphine) complex, 10-Bn-PMe3. This facile substitution of PMe3 by N2 has been previously observed for a series of diaryl imine Fe(II) complexes.12 3.9. Reaction of 9 with Chelating Alkyllithium Reagents One possible means of displacing one of the PMe3 ligands is to use an alkyllithium reagent with a pendant donor group. 2-Picolyllithium was chosen on the basis of the potential for replacement of PMe3 with pyridine, a weaker σ donor, which might increase the compound’s reactivity with olefins. Treatment of 9 with a solution of picolyllithium in Et2O gave 10-pic-N2 in 62 % yield as a red-orange residue (Eq. 3.11). Nearly identical spectroscopic data as 10-Me-N2 and 10-Bn-N2 were observed, with two coupled 31P resonances (2JPP = 124 Hz), a 13C Fe=C resonance at 313.92 ppm, and a prominent N-N stretch at 2056 cm-1 in the IR. Unfortunately, binding of the pyridine to Fe was not observed. Several explanations include the flexibility of the picolyl group, the size of the chelate that would be formed upon pyridine binding, and 86 the undoubtedly strong affinity of PMe3 for Fe(IV). In order to address some of these potential issues, (dialkylphosphino)methyllithium compounds, R2PCH2Li, were chosen as nucleophiles. These alkyllithium reagents can be readily synthesized from reaction of the corresponding dialkylmethylphosphines with tBuLi in hydrocarbon solvents. Treatment of 9 with Me2PCH2Li in Et2O/THF afforded 11-CH2PMe2 as a crystalline magenta solid in 75 % yield (Eq. 3.12). The data is consistent with a structure for 11CH2PMe2 in which one of the PMe3 ligands has been displaced by the phosphine of the lithium reagent. The 31P NMR spectrum shows 3 different phosphine resonances, each with 2 coupling partners. The 13C chemical shift for the Fe=C resonance is 305.8 ppm. Remarkably, this is the most upfield-shifted Fe=13C resonance when compared to all literature reported iron alkylidene complexes. Similarly, 9 can be treated with (methylphenylphosphino)methyllithium, MePhPCH2Li, and (diphenylphosphino)methyllithium, Ph2PCH2Li, to give the analogous compounds 11-CH2PMePh and 11-CH2PPh2, respectively, as magenta solids (Eq. 3.13 and 3.14). For 11-CH2PMePh, two isomers are formed in a 1.4:1 ratio. Given the rigid structure proposed for 11-CH2PMePh, the isomers arise from the two possible spatial orientations for the methyl and phenyl groups on the chelating 87 phosphine. For 11-CH2PPh2, there is a marked decrease in stability, as the compound gradually decomposes over the course of days under ambient conditions in C6D6. This could be a consequence of the bulkier phosphine, which could be more susceptible to dissociation to form an unstable Fe(IV) alkylidene fragment. Attempts to trap this hypothetical intermediate with an excess of styrene resulted in no noticeable change in the rate of decomposition, in addition to no new organic products. 3.10. Reaction of 4 with Mesityllithium One additional way to potentially displace a phosphine ligand is to use a bulky anionic nucleophile. This idea was tested by treating compound 9 with mesityllithium, MesLi, in Et2O, which afforded a dark red solid. While the NMR spectra showed formation of at least two products, the major product matched the spectra of 11- 88 CH2PMe2 exactly. This could be an indication that MesLi is too bulky a nucleophile to attack the imine. Instead, it is a strong enough base to deprotonate a bound trimethylphosphine ligand, which then attacks the imine, as shown in Scheme 3.5. There is literature precedent for deprotonation of a coordinated PMe3 ligand, though examples are sparse.18 Scheme 3.5. Proposed mechanism for reaction of 9 with MesLi. 3.11. Reaction of 4 with Grignard Reagents In order to expand the scope of nucleophiles, Grignard reagents were investigated. As a proof of concept, methylmagnesium chloride was chosen to see whether production of 10-Me would be observed. Treatment of 9 with MeMgCl in Et2O resulted in a red-purple solution. The isolated residue exhibited high solubility 89 in pentane. NMR spectroscopic analysis showed that the major product was a new Fe(IV) methyl complex, 12 (Eq. 3.15). Notable evidence includes a singlet at -1.48 ppm in the 31P NMR, which supports a Cs-symmetric structure, and a methyl resonance at -0.65 ppm in the 1H NMR that appears as a triplet (3JH-P = 11 Hz). This upfield shifted 1H NMR resonance is typical for iron methyl complexes. Scheme 3.6. Possible degradation pathways for 12. Other than tetrakis(1-norbornyl)iron, compound 12 is only the second example 90 of an Fe(IV) alkyl complex.19 Unfortunately, gradual decomposition of 12 to unidentified paramagnetic products over the course of 2 d precluded X-ray diffraction studies. This is not surprising given the possible reaction pathways for Compound 7, including alkylidene insertion into the Fe methyl or reductive elimination of Ar-CH3 (Scheme 3.6). In the former case, the resultant tertiary alkyl could react via two distinct β-hydride elimination pathways. The resultant iron hydrides could then undergo reductive elimination to give Fe0 complexes. 3.12. Future Directions in Fe(IV) Alkylidene Synthesis. The synthesis of catalytically active iron(IV) alkylidene complexes requires several modifications to the present system. One problem that needs to be addressed is the sterics of the alkylidene carbon. Even when we suspect that phosphine dissociation is operative, as for complex 11-CH2PPh2, the disubstituted alkylidene carbon may prevent metallocyclobutane formation upon olefin binding. One means of addressing this challenge is to allow for the convenient installation of smaller vinyl groups on iron. Scheme 3.7 shows a potential pathway for this transformation. The first step is the installation of a bidentate aryl imine ligand via oxidative addition of an imino aryl chloride to Fe(PMe3)4, as reported previously.20 Displacement of the chloride ligand with a vinyl Grignard reagent, followed by protonation, would give a cationic alkylidene complex. Treatment of the alkylidene complex with LiCH2PPh2 could afford a complex with a labile phosphine as well as a less bulky alkylidene group. Another major problem with the current iron alkylidene complexes is that they 91 Scheme 3.7. Proposed synthesis of Fe(IV) complex with less hindered alkylidene. are 18-electron complexes. Since the accepted mechanism of Grubbs’ ruthenium catalysts involves the formation of a 14-electron alkylidene intermediate, it is worthwhile to target low-coordinate iron alkylidene complexes. Scheme 3.8 shows one example of a potential route to a 14-electron iron alkylidene complex. A divinyl bis(N-heterocyclic carbene) iron complex could potentially be synthesized by treatment of a suitable iron dichloride precursor with a vinyl Grignard reagent, in analogy to the reported synthesis of a bis(N-heterocyclic carbene) iron dimethyl Scheme 3.8. Proposed synthesis of a 14-electron Fe alkylidene complex. complex.21 Protonation of this divinyl iron complex would give a cationic 14-electron 92 iron alkylidene complex, which may react more readily with olefins. Conclusion A tetradentate bis(vinylpyridine) ligand was successfully metalated with cis- Me2Fe(PMe3)4 to give a divinyl iron(II) complex, 6-PMe3. 6-PMe3 was protonated with Brookhart’s acid to give the desired cationic iron(IV) alkylidene complex. A switch to a tridentate ligand framework was demonstrated by successful metalation of an aryl-imino-alkyne ligand to give another vinyl iron(II) complex, 7. 7 was protonated to give the corresponding cationic alkylidene complex, 9. Attack at the imine carbon by several anionic nucleophiles, including methyllithium, benzyl potassium, 2-picolyllithium, and dialkylphosphino methyllithium reagents, allowed access to a rare series of neutral iron(IV) alkylidene complexes. In the case of the dialkylphosphino methyllithium reagents, the phosphine displaced a bound PMe3 to generate a tetradentate ligand framework. When methylmagnesium chloride was used as the nucleophile, a novel iron(IV) methyl complex, 12, was generated, though it proved to be unstable in solution. All attempts at olefin metathesis catalysis with these cationic and neutral alkylidene complexes were fruitless, likely due to recalcitrant phosphine dissociation as well as the steric hindrance of the alkylidene carbon, which does not allow for olefin binding and further reaction. Though catalysis was unsuccessful, this work further advances the protonation of iron(II) vinyl complexes as a viable route to iron(IV) alkylidene complexes and expands the collection of neutral iron(IV) alkylidenes. 93 Experimental General Considerations. All manipulations were performed using either glovebox or high vacuum line techniques. All glassware was oven dried. THF and ether were distilled under nitrogen from purple sodium benzophenone ketyl and vacuum transferred from the same prior to use. Hydrocarbon solvents were treated in the same manner with the addition of 1-2 mL/L tetraglyme. Benzene-d6 and was dried over sodium, vacuum transferred and stored over sodium. THF-d8 was dried over sodium and vacuum transferred from sodium benzophenone ketyl prior to use. All chemicals were commercially available and used as received. NMR spectra were obtained using an INOVA 400 MHz and 500 MHz spectrometers. Chemical shifts are reported relative to chloroform-d (1H δ 7.26; 13C{1H} δ 77.16), benzene-d6 (1H δ 7.16; 13C{1H} δ 128.39), and THF-d8 (1H δ 3.58; 13C{1H} δ 67.57). Multidimensional techniques were conducted using INOVA software affiliated with the spectrometers. Magnetic measurements obtained in solution were conducted via Evans' method in benzene-d6. Procedures. 1. 2-(2-propynyl)aniline. A 50 mL flask was charged with 2-iodoaniline (2.190 g, 10.0 mmol), CuI (0.190 g, 0.998 mmol), and PdCl2(PPh3)2 (0.281 g, 0.400 mmol). NEt3 (25 mL) was transferred to the flask, resulting in a yellow suspension upon warming to 20 °C. The flask was opened to a 1 L flask containing 2-propyne (490 mm Hg, 26.8 mmol). Within minutes, the formation of a black precipitate was evident, and the mixture was stirred for at 20 °C for 48 hr. The volatiles were removed in vacuo to give a black oily residue. Ethyl acetate (75 mL) was added to the residue, 94 and the black suspension was filtered through Celite to give a yellow solution. Volatiles were removed in vacuo and the product was vacuum distilled (50 °C) as a light yellow oil (1.01 g, 77 % yield). 1H NMR (CDCl3): δ 2.11 (s, CH3), 4.16 (br s, NH2), 6.66 (td, 7.5 Hz, 1 Hz, 1H), 6.68 (d, 8 Hz, IH), 7.08 (td, 8 Hz, 1 Hz, 1H), 7.24 ppm (dd, 7.5 Hz, 1 Hz, 1H). 2. N-benzylidene-2-propynylaniline, (pipa)H. A 25 mL flask was charged with 2-propynylaniline (250 mg, 1.91 mmol), benzaldehyde (202 mg, 1.90 mmol), CH2Cl2 (6 mL), and 4 Å molecular sieves. The mixture was stirred for 36 hr, filtered, and washed with dry CH2Cl2 (3 x 10 mL). The volatiles were removed in vacuo to afford the product as a yellow oil (345 mg, 83 % yield). 1H NMR (CDCl3): δ 2.03 (s, 3H), 7.01 (dd, 8 Hz, 1 Hz, 1H), 7.12 (td, 8 Hz, 1 Hz, 1H), 7.29 (td, 8 Hz, 2 Hz, 1H), 7.46 (m, 2H), 7.49 (m, 2H), 7.95 (m, 2H), 8.46 ppm (s, Im C-H, 1H). 13C NMR (C6D6): δ 4.32, 78.37, 90.22, 117.79, 119.98, 125.19, 128.62, 128.86, 129.30, 131.44, 133.45, 137.00, 154.77, 161.72 ppm. 3. (phimv)Fe-N2, 7. A 100 mL flask was charged with (pipa)H (400 mg, 1.82 mmol) and 15 mL benzene under a N2 atmosphere. cis-Me2Fe(PMe3)4 (712 mg, 1.82 mmol) was added to the flask and the resultant mixture was stirred for 5.5 h. The solvent was removed to give a green residue. 25 mL Et2O was transferred to the flask and the resultant mixture filtered. The filter cake was extracted with Et2O until washings were colorless. The filtrate was stripped to a dark green crystalline solid (694 mg, 81.2 % yield). 1H NMR (C6D6): δ 0.54 (br s, 18H), 2.42 (s, CH3, 3H), 2.46 (s, CH3, 3H), 6.80 (t, 7.5 Hz, Ph, 1H), 7.02-7.12 (m, Ph, 3H), 7.22 (t, 7 Hz, Ph, 1H), 7.60 (d, 7.5 Hz, Ph, 1H), 7.72 (d, 8 Hz, Ph, 1H), 8.37 (t, 4JHP = 5 Hz, NCH, 1H), 8.45 95 (d, 7 Hz, Ph, 1H). 13C NMR (C6D6): δ 12.94 (t, 2JCP, PMe3), 26.87 (CH3), 31.20 (CH3), 113.33 (Ph CH), 120.52 (Ph CH), 123.32 (Ph CH), 125.99 (Ph CH), 126.79 (Ph CH), 128.59 (Ph CH), 129.12 (Ph CH), 137.68 (t, 3JCP = 3 Hz, Ph), 137.77 (Ph CH), 148.30 (h), 151.10 (Ph), 151.44 (=CMe2), 157.29 (t, 3JCP = 4 Hz, C=N), 167.91 (t, 2JCP = 24 Hz, vinyl C-Fe), 212.74 (t, 2JCP = 17 Hz, aryl C-Fe). 31P NMR (C6D6): δ 20.56. IR (C6D6): ν(N2) = 2046 cm-1. Anal. for C23H33FeN3P2 (calc.) C 58.86, H 7.09, N 8.95; (found) C 58.62, H 7.15, N 8.96. 4. (phimalk)Fe(PMe3)3, 9. A 100 mL flask was charged with 7 (450 mg, 0.959 mmol) and [H(OEt2)2][BArF4] (970 mg, 0.958 mmol). PMe3 (0.963 mmol) was frozen in at 77 K using a 110 mL gas bulb. Et2O (40 mL) was frozen in at 77 K and the resultant mixture was warmed to -78 °C. The mixture was slowly allowed to warm to 23 °C and stirred for 16 h to give a dark red solution with solid. The solvent was removed and 25 mL pentane transferred to the flask. The red suspension was filtered and washed with pentane (5 x 10 mL) to give a dark red powder (1.090 g, 82 % yield). Slow evaporation of a hexanes/Et2O solution resulted in dark red crystals suitable for single-crystal X-ray diffraction. 1H NMR (THF-d8): δ 0.60 (t, 2JHP = 4 Hz, PMe3, 18H), 1.61 (d, 2JHP = 6 Hz, PMe3, 9H), 1.79 (d, 7 Hz, iPr CH3, 6H), 5.28 (sept, 7 Hz, iPr CH, 1H), 7.43 (t, 7 Hz, Ph, 1H), 7.46 (t, 7 Hz, Ph, 1H), 7.58 (br s, BArF4, 4H), 7.59 (m, Ph, 1H), 7.78 (t, 8 Hz, Ph, 1H), 7.80 (br s, BArF4, 8H), 8.08 (d, 8 Hz, Ph, 1H), 8.20 (d, 8 Hz, Ph, 1H), 8.30 (d, 7.5 Hz, Ph, 1H), 8.67 (d, 8 Hz, Ph, 1H), 9.73 (br s, Im C-H, 1H). 13C NMR (THF-d8): δ 17.65 (t, 2JCP = 13 Hz, PMe3), 21.67 (m, PMe3), 21.74 (iPr CH3), 55.70 (d, 3JCP = 8 Hz, iPr CH), 117.26 (Ph CH), 118.37 (BArF4), 120.03 (Ph CH), 125.68 (q, 1JCF = 272 Hz, BArF4), 126.78 (Ph CH), 128.21 96 (t, 3JCP = 3 Hz, Ph CH), 129.74 (Ph CH), 129.88 (Ph CH), 130.21 (q, 2JCF = 32 Hz, BArF4), 133.61 (Ph CH), 135.78 (BArF4), 145.22 (Ph CH), 150.68 (dt, 3JCP = 6, 2 Hz, Ph), 152.52 (Ph), 152.82 (Ph), 162.98 (q, 1JCB = 49 Hz, BArF4), 165.07 (C=N), 203.38 (td, 2JCP = 31, 14 Hz), 348.4 (C=Fe). 31P NMR (THF-d8): δ 4.13-5.84 (m). Anal. for C58H55BF24FeNP3 (calc.) C 50.42, H 4.01, N 1.01; (found) C 52.17, H 4.51, 1.13. 5. 2-picolyllithium. A flask was charged with 2-picoline (3.0 mL, 30 mmol). 25 mL Et2O was transferred and the colorless solution was cooled to -25 °C under Ar. nBuLi was added dropwise, resulting in a bright orange solution. Within minutes, an orange precipitate was apparent. The mixture was stirred at -25 °C for 45 min, cooled to -60 °C, and filtered. The orange precipitate was triturated with 10 mL pentane to give a fine bright yellow powder (1.56 g, 52 % yield). 1H NMR (THF-d8): δ 2.46 (1H, s), 2.49 (1H, s), 4.51 (1H, t, 5 Hz), 5.43 (1H, d, 9 Hz), 5.80 (1H, t, 7 Hz), 6.63 (1H, d, 5 Hz). 6. (dimethylphosphino)methyllithium, Me2PCH2Li. A solution of PMe3 (2.0 mL, 20 mmol) in 6 mL hexanes was added dropwise under Ar to a flask containing tBuLi (11.0 mL, 1.7 M in pentane, 18.7 mmol), resulting in a colorless solution with some precipitate. The mixture was stirred for 24 h, cooled to -78 °C, filtered, and washed once with pentane to give an off-white solid (0.737 g, 48 %). 1H NMR (THF-d8): δ -0.92 (2H, s, CH2Li), 0.74 ppm (6H, s, Me). 31P NMR (THF-d8): δ -40.70 ppm (s). 7. (methylphenylphosphino)methyllithium, MePhPCH2Li. A solution of tBuLi (9.0 mL, 1.7 M in pentane, 15 mmol) was added to a 50 mL flask. Dimethylphenylphosphine (2.11 g, 15.3 mmol) was added dropwise under Ar, 97 resulting in a yellow solution. The mixture was stirred at 23 °C for 24 h to afford a yellow precipitate, which was collected by filtration and washed with pentane (2 x 5 mL) to give the product as a white solid. 1H NMR (THF-d8): δ -0.65 (2H, s, CH2Li), 1.02 (3H, d, Me), 6.86 (1H, t, 7 Hz, Ph CH), 7.03 (2H, t, 7 Hz, Ph CH), 7.48 ppm (2H, m, Ph CH). 31P NMR (THF-d8): δ -18.86 ppm (s). 8. (diphenylphosphino)methyllithium, Ph2PCH2Li. A solution of tBuLi (5.0 mL, 1.7 M in pentane, 8.5 mmol) was added to a 50 mL flask. Methyldiphenylphosphine (1.73 g, 8.62 mmol) was added dropwise under Ar, resulting in a pale yellow solution. The mixture was stirred at 23 °C for 2 d, resulting in the formation of a white precipitate, which was collected by filtration and washed with pentane (2 x 10 mL) to give the desired product as a white solid. 1H NMR (THFd8): δ -0.38 (2H, s, CH2Li), 6.89 (2H, m, Ph CH), 7.01 (4H, m, Ph CH), 7.46 ppm (4H, m, Ph CH). 31P NMR (THF-d8): δ 3.46 ppm (s). 9. 10-Me-N2. A flask was charged with 9 (100 mg, 0.072 mmol) and 4 mL Et2O, affording a dark red solution. The solution was cooled to -78 °C under an Ar atmosphere. A solution of MeLi (0.36 mL, 0.20 M in Et2O, 0.072 mmol) was added dropwise, resulting in no apparent color change. The solution was allowed to slowly warm to 23 °C and was stirred for 12 h, giving a red-brown solution. The solvent was removed in vacuo and the resulting residue triturated with pentane (2 x 5 mL). Under a N2 atmosphere, 5 mL pentane was added to the residue and the resulting mixture filtered through Celite and stripped to a red residue (25 mg, 72 % yield). 1H NMR (C6D6): δ 0.31 (9H, d, 8 Hz, PMe3), 0.56 (9H, d, 8 Hz, PMe3), 1.47 (3H, d, 6.5 Hz, NCH(CH3)), 1.55 (3H, d, 7 Hz, iPr CH3), 1.73 (3H, d, 7 Hz, iPr CH3), 4.60 (1H, sept, 7 98 Hz, iPr CH), 4.96 (1H, m, NCH), 6.28 (1H, dd, 8 Hz, 6.5 Hz, Ph CH), 6.70 (1H, d, 9 Hz, Ph CH), 6.84 (1H, t, 7.5 Hz, Ph CH), 7.05 (1H, d, 7.5 Hz, Ph CH), 7.26 (1H, t, 7 Hz, Ph CH), 7.35 (1H, t, 7 Hz, Ph CH), 7.40 (1H, d, 9 Hz, Ph CH), 8.13 (1H, d, 6.5 Hz, Ph CH). 13C NMR (C6D6): δ 13.93 (d, 24 Hz), 15.35 (d, 23 Hz), 22.36, 24.72 (d, 28 Hz), 30.26, 44.12, 64.45, 110.45, 114.36 (t, 3.5 Hz), 119.67, 121.36 (t, 3 Hz), 122.92 (t, 3 Hz), 125.30 (t, 3 Hz), 130.37, 136.85, 148.66, 157.03, 168.07, 181.29 (t, 29 Hz), 313.77 (t, 14 Hz). 31P NMR (C6D6): δ 12.98 (1P, d, 125 Hz), 15.05 (1P, d, 125 Hz). IR: νN2 (C6D6) = 2058 cm-1. 10. 10-Bn-N2. A 10 mL flask was charged with benzyl potassium (10 mg, 0.077 mmol) and 9 (106 mg, 0.077 mmol). 5 mL THF was transferred to the flask in vacuo. The mixture was slowly allowed to warm from -78 °C to 23 °C and stirred for 12 h. The resultant red-purple solution was stripped to a magenta solid. Under a N2 atmosphere, hexanes (6 mL) was added to the solid. The mixture was filtered through Celite and stripped to a red-brown oil. 1H NMR (C6D6): δ 0.27 (9H, d, 8 Hz, PMe3), 0.69 (9H, d, 8 Hz, PMe3), 1.58 (3H, d, 7 Hz, iPr CH3), 1.77 (3H, d, 7 Hz, iPr CH3), 2.57 (1H, dd, 13 Hz, 11 Hz, Ph-CH2), 3.67 (1H, d, 13 Hz, Ph-CH2), 4.66 (1H, sept, 7 Hz, iPr CH), 5.39 (1H, m, N-CH(Bn)), 6.33 (1H, t, 7 Hz, Ph CH), 6.51 (1H, d, 7 Hz, Ph CH), 6.94 (1H, m, Ph CH), 6.97 (1H, m, Ph CH), 7.10 (1H, d, 9 Hz, Ph CH), 7.18 (1H, m, Ph CH), 7.27 (3H, m, Ph CH), 7.35 (2H, d, 7 Hz), 7.45 (1H, d, 8 Hz, Ph CH), 8.13 ppm (br d, 7 Hz, Ph CH). 13C NMR (C6D6): δ 13.76 (d, 23 Hz, PMe3), 15.79 (d, 24 Hz, PMe3), 24.69, 24.92, 43.15, 44.33, 70.94, 110.69, 113.86 (t, 4 Hz), 119.80, 122.28 (t, 3 Hz), 122.69 (t, 3 Hz), 125.55 (t, 4 Hz), 126.57, 128.78, 130.24, 130.74 (t, 2 Hz), 136.94 (t, 3 Hz), 140.44, 148.68 (d, 2 Hz), 154.59 (t, 2 Hz), 167.75 (dd, 6 Hz, 3 99 Hz), 181.36 (t, 28 Hz, Fe-Caryl), 315.54 ppm (t, 14 Hz, Fe=C). 31P NMR (C6D6): δ 12.72 (d, 127 Hz), 15.08 ppm (d, 127 Hz). IR: ν(N2) = 2058 cm-1. 11. 10-Bn-PMe3. A 25 mL flask was charged with 9 (117 mg, 0.0847 mmol) and benzyl potassium (11 mg, 0.084 mmol). 5 mL Et2O was transferred to the flask. The mixture was allowed to slowly warm from -78 °C to 23 °C and was stirred for 12 h, resulting in a red-purple solution. The solvent was removed in vacuo to give a dark red-purple solid. 8 mL pentane was transferred to the flask and the mixture was filtered. The filter cake was washed with pentane (4 x 8 mL) until extracts were no longer red. The solvent was removed to give a magenta solid (44 mg, 86 % yield). C6D6 (0.5 mL) was transferred to the flask and the resultant solution was added under Ar to a J-Young tube. 1H NMR (C6D6): δ 0.20 (9H, d, 7 Hz, PMe3), 0.74 (9H, d, 7 Hz, PMe3), 1.22 (9H, d, 5 Hz, PMe3), 1.66 (3H, d, 7 Hz, iPr CH3), 1.71 (3H, d, 7 Hz, iPr CH3), 2.59 (1H, “t”, 12 Hz, Bn CH2), 3.97 (1H, “t”, 12 Hz, Bn CH2), 4.76 (1H, sept, 7 Hz, iPr CH), 5.37 (1H, m, NCHBn), 6.37 (1H, t, 7 Hz, Ar CH), 6.50 (1H, d, 7 Hz, Ar CH), 6.98 (1H, t, 6.5 Hz, Ar CH), 7.07 (1H, t, 6.5 Hz, Ar CH), 7.22-7.35 (4H, m, Ar CH), 7.44 (2H, d, 7 Hz, Ar CH), 7.59 (1H, d, 8.5 Hz, Ar CH), 7.97 ppm (1H, “d”, 7 Hz, Ar CH). 31P NMR (C6D6): δ 7.54 (dd, 92 Hz, 70 Hz), 9.34 (dd, 70 Hz, 53 Hz), 12.36 ppm (dd, 92 Hz, 53 Hz). 12. 10-pic-N2. A 25 mL flask was charged with 9 (250 mg, 0.181 mmol) and 6 mL Et2O, affording a dark red solution. The solution was cooled to -78 °C under Ar. A solution of 2-picolyllithium (18 mg, 0.18 mmol) in 2 mL thf was added dropwise, resulting in a red-orange solution. The solution was allowed to warm to 23 °C and was stirred for 12 h. Solvent was removed and the resultant residue triturated with 100 pentane (2 x 8 mL) to give a red solid. The product was extracted with 10 mL hexanes under N2 and filtered through Celite. The resultant dark red solution was stripped to give an oily red-orange solid (63 mg, 62 % yield). 1H NMR (C6D6): δ 0.28 (9H, d, 8 Hz, PMe3), 0.70 (9H, d, 8 Hz, PMe3), 1.59 (3H, d, 7 Hz, iPr CH3), 1.77 (3H, d, 7 Hz, iPr CH3), 2.82 (1H, dd, 13 Hz, 9 Hz, pic CH2), 3.89 (1H, d, 13 Hz, pic CH2), 4.65 (1H, sept, 7 Hz, iPr CH), 6.04 (1H, t, 7.5 Hz), 6.31 (1H, t, 7 Hz), 6.58 (1H, d, 7 Hz), 6.70 (1H, t, 6 Hz), 6.78 (1H, d, 7 Hz), 6.98 (1H, t, 7.5 Hz), 7.02 (1H, t, 7 Hz), 7.08 (1H, t, 7 Hz), 7.30 (1H, t, 7 Hz), 7.43 (1H, d, 8.5 Hz), 7,87 (1H, d, 9 Hz), 8.16 (1H, d, 6.5 Hz), 8.68 (1H, d, 4 Hz). 13C NMR (C6D6): δ 13.84 (d, 23 Hz), 15.68 (d, 23 Hz), 24.74, 24.97, 31.98, 44.20, 46.17, 69.78, 111.01, 115.29 (t, 4 Hz), 119.69, 121.24, 121.60 (t, 3 Hz), 122.50 (t, 3 Hz), 124.84, 125.38 (t, 3.5 Hz), 130.97, 135.75, 137.04, 148.62, 150.26, 156.17, 160.99, 168.37 (dd, 6 Hz, 3 Hz), 181.79 (t, 28 Hz, Fe-Caryl), 313.93 (t, 13 Hz, Fe=C). 31P NMR (C6D6): δ 13.04 (1P, d, 124 Hz), 14.96 (d, 124 Hz). IR: νN2 (C6D6) = 2056 cm-1. 13. 11-CH2PMe2. A 10 mL flask was charged with 9 (59 mg, 0.043 mmol) and 2 mL thf, affording a dark red solution. The solution was cooled to -78 °C under Ar. A solution of Me2PCH2Li (0.50 mL, 0.088 M in thf, 0.044 mmol) was added dropwise. The solution was allowed to slowly warm to 23 °C and stirred for 6 h. Solvent was removed to give a magenta residue, which was triturated with pentane (5 mL). Under N2, hexanes (5 mL) was added to the solid. The mixture was filtered through Celite and stripped to a magenta solid. 1H NMR (C6D6): δ 0.39 (3H, d, 8 Hz), 0.54 (12H, d, 6 Hz), 1.20 (9H, d, 6 Hz), 1.62 (3H, d, 7 Hz), 1.68 (1H, t, 4.5 Hz), 1.71 (1H, t, 4.5 Hz), 1.86 (3H, d, 7 Hz), 4.62 (1H, sept, 7 Hz), 5.53 (1H, dd, 25 Hz, 4.5 101 Hz), 6.38 (1H, m), 7.01 (2H, m), 7.20-7.31 (3H, m), 7.66 (1H, d, 9 Hz), 7.97 (1H, m). 13C NMR (C6D6): δ 17.09 (d, 22.5 Hz), 19.29 (d, 24 Hz), 20.19 (d, 16 Hz), 22.81, 23.08 (d, 16 Hz), 23.46, 41.99 (dd, 47 Hz, 6 Hz), 47.54 (9.5 Hz), 66.94 (4.5 Hz), 109.83, 111.63, 118.60 (t, 3 Hz), 120.35, 123.14 (t, 3 Hz), 124.06 (t, 3 Hz), 127.19, 144.90 (d, 5 Hz), 148.35 (d, 6 Hz), 157.11 (dd, 9 Hz, 3 Hz), 166.71, 177.67 (td, 38 Hz, 7 Hz, Fe-Caryl), 305.79 (td, 18 Hz, 11 Hz, Fe=C). 31P NMR (C6D6): δ 12.97 (dd, 92 Hz, 57 Hz), 21.62 (dd, 57 Hz, 53 Hz), 39.52 (dd, 92 Hz, 53 Hz). 14. 11-CH2PMePh. A 25 mL flask was charged with 9 (96 mg, 0.069 mmol) and 5 mL Et2O. The dark red solution was cooled to -78 °C. A solution of PhMePCH2Li (10 mg, 0.069 mmol) in 2 mL THF was added dropwise, resulting in a dark red-purple solution. The mixture was allowed to slowly warm to 23 °C overnight, then was stripped to a dark red solid. 5 mL hexanes was added to the flask and the resultant mixture was filtered through Celite and stripped to a dark red residue. 31P NMR (C6D6): δ 12.43 (dd, 87 Hz, 58 Hz, minor), 13.82 (dd, 87 Hz, 59 Hz, major), 19.22 (dd, 58 Hz, 49 Hz, minor), 20.08 (dd, 59 Hz, 48 Hz, major), 40.48 (dd, 87 Hz, 48 Hz, major), 41.67 ppm (dd, 87 Hz, 49 Hz, minor). 15. 11-CH2PPh2. A 25 mL flask was charged with 9 (200 mg, 0.145 mmol) and Ph2PCH2Li (30 mg, 0.15 mmol). 6 mL Et2O was transferred to the flask at -78 °C. The mixture was allowed to warm to 23 °C and was stirred for 12 h. The dark red solution was stripped to a red solid. Hexanes (10 mL) was transferred to the flask and the mixture filtered. The filter cake was washed with hexanes until extracts were colorless. The filtrate was stripped to give an oily red residue. 31P NMR (C6D6): δ 13.35 (dd, 86 Hz, 59 Hz), 17.42 (dd, 59 Hz, 43 Hz), 56.62 ppm (86 Hz, 43 Hz). 102 16. Compound 12. 9 (50 mg, 0.036 mmol) and Et2O (2 mL) were added to a 10 mL flask. The resultant dark red solution was cooled to -78 °C and opened to an Ar atmosphere. MeMgCl (0.35 mL, 0.104 M in Et2O, 0.036 mmol) was added dropwise to the flask. The mixture was allowed to warm to 23 °C and was stirred for 6 h. The resultant red-brown solution was stripped to a red-brown solid. Pentane (2 mL) was added and the mixture was filtered through Celite and stripped to a green residue. 1H NMR (C6D6): δ -0.65 (3H, t, 3JHP = 11 Hz, Fe-CH3), 0.32 (18H, t, 4 Hz, PMe3), 1.65 (6H, t, 7 Hz, iPr CH3), 5.10 (1H, m, iPr CH), 6.95 (1H, t, 7.5 Hz), 7.05 (1H, d, 8 Hz), 7.35 (1H, t, 7.5 Hz), 7.46 (1H, t, 8 Hz), 7.62 (1H, t, 7.5 Hz), 7.96 (1H, d, 8 Hz), 8.19 (1H, d, 8 Hz), 8.52 (1H, d, 7.5 Hz), 9.54 ppm (1H, s, N=CH). 13C NMR (C6D6): δ -21.88 (t, 35 Hz), 13.95 (t, 11.5 Hz), 17.77 (t, 4 Hz), 52.49 (t, 2 Hz), 112.25 (s), 114.05 (s), 115.36 (t, 3 Hz), 122.45 (t, 2 Hz), 122.94 (t, 4 Hz), 125.05 (t, 3 Hz), 128.89 (s), 129.04 (s), 129.41 (t, 3 Hz), 141.76 (t, 3 Hz), 154.91 (t, 3 Hz), 208.87 (t, 37.5 Hz), 321.15 ppm (t, 30.5 Hz). 31P NMR (C6D6): δ -1.48 ppm (s). 103 REFERENCES (1) Klein, H.-F.; Camadanli, S.; Beck, R.; Florke, U. Chem. Commun. 2005, No. 3, 381–382. (2) Klein, H.-F.; Camadanli, S.; Beck, R.; Leukel, D.; Flörke, U. Angew. Chem. Int. Ed. 2005, 44 (6), 975–977. (3) Beck, R.; Sun, H.; Li, X.; Camadanli, S.; Klein, H.-F. Eur. J. Inorg. Chem. 2008, 2008 (21), 3253–3257. (4) Beck, R.; Zheng, T.; Sun, H.; Li, X.; Flörke, U.; Klein, H.-F. J. Organomet. Chem. 2008, 693 (23), 3471–3478. (5) Camadanli, S.; Beck, R.; Flörke, U.; Klein, H.-F. Organometallics 2009, 28 (7), 2300–2310. (6) Xu, G.; Sun, H.; Li, X. Organometallics 2009, 28 (20), 6090–6095. (7) Liu, N.; Li, X.; Sun, H. J. Organomet. Chem. 2011, 696 (13), 2537–2542. (8) Wu, S.; Li, X.; Xiong, Z.; Xu, W.; Lu, Y.; Sun, H. Organometallics 2013, 32 (11), 3227–3237. (9) Zhao, H.; Sun, H.; Li, X. Organometallics 2014, 33 (13), 3535–3539. (10) Volpe, E. C.; Wolczanski, P. T.; Lobkovsky, E. B. Organometallics 2010, 29 (2), 364–377. (11) Volpe, E. C.; Wolczanski, P. T.; Darmon, J. M.; Lobkovsky, E. B. Polyhedron 2013, 52, 406–415. (12) Bartholomew, E. R.; Volpe, E. C.; Wolczanski, P. T.; Lobkovsky, E. B.; Cundari, T. R. J. Am. Chem. Soc. 2013, 135 (9), 3511–3527. (13) Brookhart, M.; Grant, B.; Volpe, A. F. Organometallics 1992, 11 (11), 3920– 3922. (14) Klose, A.; Hesschenbrouck, J.; Solari, E.; Latronico, M.; Floriani, C.; Re, N.; Chiesi-Villa, A.; Rizzoli, C. J. Organomet. Chem. 1999, 591 (1–2), 45–62. (15) Li, Y.; Huang, J.-S.; Zhou, Z.-Y.; Che, C.-M.; You, X.-Z. J. Am. Chem. Soc. 2002, 124 (44), 13185–13193. (16) Mahias, V.; Cron, S.; Toupet, L.; Lapinte, C. Organometallics 1996, 15 (25), 5399–5408. 104 (17) Brookhart, M.; Studabaker, W. B.; Humphrey, M. B.; Husk, G. R. Organometallics 1989, 8 (1), 132–140. (18) van der Eide, E. F.; Piers, W. E.; Parvez, M.; McDonald, R. Inorg. Chem. 2007, 46 (1), 14–21. (19) Bower, B. K.; Tennent, H. G. J. Am. Chem. Soc. 1972, 94 (7), 2512–2514. (20) Shi, Y.; Li, M.; Hu, Q.; Li, X.; Sun, H. Organometallics 2009, 28 (7), 2206– 2210. (21) Hashimoto, T.; Urban, S.; Hoshino, R.; Ohki, Y.; Tatsumi, K.; Glorius, F. Organometallics 2012, 31 (12), 4474–4479. 105 Appendix 1 Vinyl and Imine C-H Activation Attempts with cis-Me2Fe(PMe3)4 Introduction In the efforts toward generating Fe(II) vinyl complexes via C-H bond activation, several alkene-containing substrates were explored for which unsuccessful or inefficient metalation with cis-Me2Fe(PMe3)4 was observed. These findings have illustrated the subtleties of cis-Me2Fe(PMe3)4-mediated metalation, as minor alterations to successfully metalated ligands often resulted in no reactivity, sluggish reactivity, or non-selective reactivity resulting in multiple products. In addition to these alkene C-H activation attempts, the activation of aldimine C-H bonds was also explored. Results and Discussion A1.1. Synthesis of Bidentate Vinyl Imine Ligand and Unsuccessful Metalation In order to explore the reactivity of bidentate alkene-containing ligand substrates with cis-Me2Fe(PMe3)4, the synthesis of vinyl imines was explored. A mixture of cinnamaldehyde and 2,6-diisopropylaniline in toluene was heated at reflux under Ar, with water removed using a Dean-Stark trap, to afford 2-(N-2,6diisopropylphenyl)iminostyrene, dippis, as a yellow crystalline solid (Eq. A1.1). Unfortunately, when dippis was treated with 1 equiv cis-Me2Fe(PMe3)4, no reaction was observed after several days at 23 °C (Eq. A1.2). It is likely that the bulky 2,6- 106 diisopropylphenyl group impedes imine binding, which is necessary for chelateassisted C-H activation. The synthesis of analogous imines bearing smaller substituents was not pursued. A1.2. Tridentate Ligands and Metalation Attempts Despite the successful metalation of several tridentate ligand frameworks with cis-Me2Fe(PMe3)4 by myself and Ala’aeddeen Swidan, failure to obtain either the desired protonation reactivity with the Fe(II) vinyl complexes or failure to observe reactivity of the alkylidenes with olefins led us to pursue similar tridentate ligands with differing steric parameters to probe changes in observed reactivity. Scheme A1.1 shows the tridentate ligands that were successfully metalated and their subsequent reactivity. One possible reason for the recalcitrant reactivity of the alkylidene complex shown in Scheme A1.1 is that the isopropyl group is too bulky to allow for metallacyclobutane formation upon olefin binding. To address this, the propynyl group was replaced by an ethynyl group. (2-aminophenyl)trimethylsilylacetylene was 107 synthesized in 55 % yield through a palladium catalyzed cross-coupling of 2iodoaniline and (trimethylsilyl)acetylene, according to literature protocol (Eq. A1.3). Scheme A1.1. Examples of successfully metalated tridentate ligands from this work (A) and from Ala’aeddeen Swidan (B, C), as well as their subsequent reactivity. Note: P = PMe3, ArF = 3,5-(CF3)2C6H3 The trimethylsilyl group can be cleaved using KF to give the free 2- ethynylaniline (Eq. A1.4). Condensation of the acetylene with benzaldehyde in CH2Cl2 with 4Å molecular sieves as the drying agent afforded N-benzylidene-2ethynylaniline, bea, in 72 % yield as a yellow oil (Eq. A1.5). Unfortunately, treatment of bea with cis-Me2Fe(PMe3)4 in C6D6 at 23 °C resulted in an intractable mixture of diamagnetic products (Eq. A1.6). This is likely a consequence of the alkyne C-H acidity, which could lead to alkynyl iron complexes via loss of methane. 108 A modification to the ligand in Scheme A1.1B in which the allylamine moiety is replaced by dimethylallylamine was next pursued. Dimethylallylamine was synthesized in 3 steps from 1,1-dimethylpropargylamine via Boc protection, Cu catalyzed partial alkyne hydrogenation (as developed by Lalic and co-workers),1 and Scheme A1.2. Synthesis of 1,1-dimethylallylamine 109 Boc deprotection (Scheme A1.2). Due to the volatility of 1,1-dimethylallylamine, the reagent was used as a solution for the subsequent condensation reaction with benzaldehyde to give N-benzylidene-1,1-dimethylallylamine, bdmaa, as a yellow oil (Eq. A1.7). Unfortunately, when bdmaa was treated with cis-Me2Fe(PMe3)4 in C6D6, no reaction was observed (Eq. A1.8). This is likely a consequence of the sterics of the gem dimethyl group, which prevents imine coordination. A2.3. Synthesis and Metalation of trans-1-(2-pyridyl)-3-phenylpropene, pyphp As an alteration of the previously mentioned ligands, we pursued tridentate ligand frameworks which have the alkene in the central position of the pincer. We first targeted trans-1-(2-pyridyl)-3-phenylpropene, pyphp. The initial synthetic route for the preparation of pyphp consisted of a three step synthesis (Scheme A1.3). The first step was with the reaction of phenethylmagnesium bromide with 2pyridinecarboxaldehyde in THF to give 1-(2-pyridyl)-3-phenylpropan-1-ol in 45 % yield. The alcohol was then converted to the corresponding tosylate by treatment with KH and tosyl chloride. The tosylate was treated with NiPr2Et in C6H6 at 120 °C to give pyphp as a light brown oil after purification by column chromatography. The 110 product contained the cis isomer as a minor impurity (~ 5 %). Scheme A1.3. Synthesis of pyphp. Since the first synthesis of pyphp requires two column purification steps, is time intensive, and is low-yielding, we sought a more efficient route using a HornerWadsworth-Emmons olefination. (2-pyridyl)diethylphosphate was treated with LiHMDS in Et2O, followed by treatment with 0.5 equiv of phenylacetaldehyde to generate pyphp cleanly as a yellow oil in 62 % yield (Eq. A1.9). In contrast to the previous synthesis, there were no observable impurities. cis-Me2Fe(PMe3)4 was treated with pyphp to give a purple solution containing a mixture of products in a 1:5:14 ratio (Eq. A1.10). Based on 31P NMR and IR spectroscopy, the product corresponding to 25 % of the mixture is likely a 111 bis(trimethylphosphine) dinitrogen complex. There is an intense IR stretch at 2038 cm-1, which is assigned to a N-N stretching mode, as well as a singlet at 17.84 ppm in the 31P NMR. The other two products appear to be tris(trimethylphosphine) complexes, as the major product has three broad resonances integrating 1:1:1 and the minor product has a doublet and triplet in a 2:1 ratio, which is common for Fe(PMe3)3 compounds. A2.4. Synthesis and Metalation of trans-2-(2,6-dimethylphenyl)-2-vinylpyridine, dmpvp Using the same Horner-Wadsworth-Emmons route as for the synthesis of pyphp, trans-2-(2,6-dimethylphenyl)-2-vinylpyridine (dmpvp), was synthesized from 2,6-dimethylbenzaldehyde, (2-pyridyl)diethylphosphonate, and LiHMDS (Eq. A1.11). 112 Metalation of dmpvp with cis-Me2Fe(PMe3)4 in C6D6 resulted in slow conversion (50 % in 4 days) to a single diamagnetic product. The product is formed via vinyl and benzylic C-H bond activation. Due to the slow conversion and the partial decomposition of the iron precursor, the reaction was not pursued. A2.5. Synthesis and Imine C-H Activation of Tridentate Ligands In analogy to our extensive efforts towards vinyl C-H activation, we also pursued the activation of imine C-H bonds. Ligands were designed so that competitive C-H activation involving binding of the imine nitrogen would be avoided. The condensation of 2,6-dimethylbenzaldehyde with 2-aminopyridine and 2-amino-6methylpyridine was carried out in CH2Cl2 with 4Å molecular sieves as the drying agent to afford (2,6-dimethylbenzylidene)-2-pyridylamine, dmbpaH2, and (2,6dimethylbenzylidene)-2-(6-methylpyridyl)amine, dmbmpaH2, as yellow oils (Eq. A1.13-14). cis-Me2Fe(PMe3)4 was treated with dmbpaH2 in benzene to give (dmbpa)FePMe3 in 74 % yield as a dark purple solid (Eq. A1.15). Likewise, cis-Me2Fe(PMe3)4 113 was treated with dmbmpaH2 in benzene to give (dmbmpa)Fe-N2 as a dark red solid in 79 % yield (Eq. A1.16). (dmbmpa)Fe-N2 has a characteristically sharp IR stretch at 2051 cm-1. This ligand substitution of PMe3 by N2 is due to the sterics of the additional methyl group. It is worth noting that when (dmbpa)Fe-PMe3 is treated with 1 atm CO, there is a slow conversion to a mixture of (dmbpa)Fe-PMe3 and (dmbpa)FeCO, as evidenced by a new singlet in the 31P NMR and an intense C-O stretch at 1878 cm-1 in the IR spectrum (Eq. A1.17). In the course of reactivity studies, (dmbmpa)Fe-N2 was treated with 1 equiv. PMe3 in the presence of H2 (1 atm) to afford A1-H as a red solid (Eq. A1.18). A1-H 114 has a characteristic hydride resonance at -27.18 ppm in the 1H NMR spectrum which appears as a triplet of doublets with 2JH-P coupling constants of 66 Hz and 44 Hz. Likewise, the 31P{1H} spectrum shows a triplet and doublet, as expected for a tris(trimethylphosphine) complex. A1-H is the product of the addition of 2 equiv H2, which results in hydrogenation of the imine fragment and hydrogenolysis of the FeC(sp3) bond (Scheme A1.4). Scheme A1.4. Proposed mechanism for the formation of A1-H. 115 Experimental General Considerations. All manipulations were performed using either glovebox or high vacuum line techniques. All glassware was oven dried. THF and ether were distilled under nitrogen from purple sodium benzophenone ketyl and vacuum transferred from the same prior to use. Hydrocarbon solvents were treated in the same manner with the addition of 1-2 mL/L tetraglyme. Benzene-d6 and was dried over sodium, vacuum transferred and stored over sodium. THF-d8 was dried over sodium and vacuum transferred from sodium benzophenone ketyl prior to use. Lithium bis(trimethylsilyl)amide was purchased from Aldrich and recrystallized from hexanes prior to use. IPrCuOtBu,2 N-Boc-1,1-dimethylpropargylamine,3 (2aminophenyl)trimethylsilylacetylene,4 and 2-ethynylaniline5 were prepared according to literature procedures. All other chemicals were commercially available and used as received. NMR spectra were obtained using an INOVA 400 MHz and 500 MHz spectrometers. Chemical shifts are reported relative to benzene-d6 (1H δ 7.16; 13C{1H} δ 128.39) and THF-d8 (1H δ 3.58; 13C{1H} δ 67.57). Multidimensional techniques were conducted using INOVA software affiliated with the spectrometers. Magnetic measurements obtained in solution were conducted via Evans' method in benzene-d6. Procedures. 1. 2-(N-2,6-diisopropylphenyl)iminostyrene, dippis.6 A 50 mL flask was charged with cinnamaldehyde (2.00 g, 15.1 mmol), 2,6-diisopropylaniline (2.68 g, 15.1 mmol), and toluene (15 mL). The flask was equipped with a Dean-Stark trap and was heated at reflux for 12 h. The solvent was removed in vacuo to give a yellow 116 solid, which was crystallized from hot EtOH to give a yellow crystalline solid. 1H NMR (CDCl3): δ 1.17 (12H, d, 7 Hz, iPr CH3), 2.97 (2H, sept, 7 Hz, iPr CH), 7.087.19 (5H, m, Ar, vy CH), 7.40 (3H, m, Ar CH), 7.57 (2H, d, 7.5 Hz, Ar CH), 7.94 ppm (1H, d, 8 Hz, vy CH). 2. N-benzylidene-2-ethynylaniline, bea.7 A 10 mL flask was charged with 2-ethynylaniline (300 mg, 2.56 mmol), benzaldehyde (283 mg, 2.67 mmol), CH2Cl2 (3 mL), and 4Å molecular sieves. The mixture was stirred at 23 °C for 2 d, then filtered and stripped to a yellow oil (375 mg, 71.5 %). A color change to brown was noted upon long term storage. 1H NMR (C6D6): δ 2.86 (1H, s, C≡C-H), 6.76 (1H, d, 9 Hz, Ar CH), 6.80 (1H, t, 8 Hz, Ar CH), 6.97 (1H, t, 8 Hz, Ar CH), 7.08-7.13 (3H, m, Ar CH), 7.53 (1H, d, 9 Hz), 7.83-7.88 (2H, m, Ar CH), 8.09 (1H, s, Im CH). 3. N-boc-1,1-dimethylallylamine.1 A flask was charged with N-boc-1,1dimethylpropargylamine (1.00 g, 5.46 mmol). 40 mL toluene was transferred to the flask in vacuo to give a colorless solution. iBuOH (0.66 mL, 7.14 mmol) and PMHS (0.450 g, 7.48 mmol) were added to the flask via syringe under Ar. IPrCuOtBu (29 mg, 0.055 mmol) was added, resulting in a pale yellow solution with some noticeable bubbling. After stirring for 2 h at 23 °C, an aliquot was analyzed by mass spectrometry, which showed no remaining starting material. 20 mL hexanes was added and the mixture was filtered through a silica gel plug, with 1:1 hexanes:EtOAc used to elute the remaining product. The solvent was removed to give a pale yellow oil. 1H NMR confirmed the presence of a silicon containing byproduct, so the mixture was twice treated with KOH (40 mmol, in 1:1 thf:H2O) for 12 h to afford the product as a yellow oil. 1H NMR (CDCl3): δ 1.36 (6H, s, CMe2), 1.43 (9H, s, tBu), 4.57 (1H, 117 br s, NH), 5.02 (1H, d, 11 Hz, vy CH), 5.09 (1H, d, 17 Hz, vy CH), 5.96 ppm (1H, dd, 17 Hz, 11 Hz, vy CH). 4. N-benzylidene-1,1-dimethylallylamine, bdmaa. A 25 mL flask was charged with N-Boc-1,1-dimethylallylamine (0.762 g, 4.11 mmol) and 6 mL CH2Cl2. The mixture was cooled to 0 °C and trifluoroacetic acid (6 mL) was added dropwise, resulting in a color change from yellow to orange. The mixture was stirred at 0 °C for 2 h then stripped to a red oil. 6 mL CH2Cl2 was added and the solution was cooled to 0 °C. 2 M NaOH was added dropwise until the mixture was basic. The layers were separated and the aqueous layer extracted once with 3 mL CH2Cl2. The combined organics were added to a 50 mL flask with 4Å molecular sieves and benzaldehyde (0.45 g, 4.24 mmol). The mixture was stirred for 24 h, filtered, and stripped to a yellow oil. 1H NMR (CDCl3): δ 1.38 (6H, s, CMe2), 5.16 (1H, dd, 11 Hz, 4 Hz, vy CH), 5.18 (1H, dd, 17 Hz, 4 Hz, vy CH), 5.94 (1H, dd, 17 Hz, 11 Hz, vy CH), 7.40 (3H, m, Ph CH), 7.76 (2H, m, Ph CH), 8.26 ppm (1H, s, Im CH). 5. 1-(2-pyridyl)-3-phenylpropan-1-ol.8 (2-bromoethyl)benzene (1.52 mL, 11.1 mmol) was added dropwise to a suspension of magnesium turnings in dry THF (12 mL). The mixture was warmed gently (~ 35 °C) for 1 h, resulting in a gray-brown suspension. THF was transferred in vacuo to a 100 mL flask. 2pyridinecarboxaldehyde (0.85 mL, 8.9 mmol) was added to the flask under Ar, resulting in a yellow solution. After cooling the solution to -78 °C, the Grignard reagent was added slowly via syringe, resulting in a color change to dark brown. The reaction mixture was allowed to slowly warm to 25 °C and stirred for 12 h. The mixture was cooled to 0 °C and 1M HCl(aq) (10 mL) was added slowly. Et2O (5 mL) 118 was added and the layers were separated. The aqueous layer was basified to pH 9 with 1M NH3(aq) and then extracted 3 times with Et2O. The combined organic extracts were dried over MgSO4, filtered, and volatiles removed in vacuo to give an orange liquid, which was purified by silica gel column chromatography with 1:1 hexanes : ethyl acetate as eluent to give a light yellow oil, which solidified upon standing (0.85 g, 45 %). 1H NMR (C6D6): δ 1.87- 2.15 (2H, m, -C(OH)H-CH2), 2.77-2.97 (2H, m, py-CH2), 4.45 (1H, d, 5 Hz, OH), 4.67-4.78 (1H, m, HOC-H), 6.57 (1H, m, py CH), 6.69 (1H, d, 8 Hz, py CH), 6.99 (1H, t, 8 Hz, py CH), 7.04-7.12 (1H, m, Ph CH), 7.18 (3H, s, Ph CH), 8.29 (1H, d, 4.5 Hz, py CH). 6. 1-(2-pyridyl)-3-phenylpropane-1-tosylate. A 100 mL flask was charged with 1-(2-pyridyl)-3-phenylpropan-1-ol (500 mg, 2.34 mmol) and KH (181 mg, 4.51 mmol). 30 mL THF was transferred to the flask, resulting in a color change from brown to red. The mixture was stirred at 23 °C under Ar for 2 h. A solution of tosyl chloride (538 mg, 2.822 mmol) in THF (10 mL) was added to the flask, resulting in a color change from green to orange-brown. The mixture was stirred at 23 °C for 12 h. The mixture was quenched with 6 drops of sat. NaHCO3(aq). Et2O (10 mL) and water (10 mL) were added and the layers were separated. The aqueous layer was extracted with Et2O (3 x 15 mL). The combined organics were dried over MgSO4, filtered, and stripped to a brown oil (0.80 g, 93 %). 1H NMR (C6D6): δ 1.76 (3H, s, Ts CH3), 2.162.39 (2H, m, CH2), 2.44-2.66 (2H, m, CH2), 5.79 (1H, dd, 7 Hz, 5 Hz, CHOTs), 6.50 (1H, ddd, 7.5 Hz, 5 Hz, 1 Hz, py CH), 6.57 (2H, “d”, 8 Hz, Ph CH), 6.90 (2H, “d”, 8 Hz, Ph CH), 6.95 (1H, td, 7.5 Hz, 2 Hz, py CH), 6.99-7.10 (3H, m, Ph CH), 7.19 (1H, td, 8 Hz, 1 Hz, py CH), 7.69 (2H, “d”, 8 Hz, Ph CH), 8.28 ppm (1H, ddd, 5 Hz, 2 Hz, 119 1 Hz, py CH). 7. trans-1-(2-pyridyl)-3-phenylpropene, pyphp.9 a. A glass bomb was charged with a solution of 1-(2-pyridyl)-3-phenylpropane-1-tosylate (1.00 g, 2.72 mmol) in C6H6 (18 mL). NiPr2Et (4.8 mL, 27.6 mmol) was added and the solution was degassed. The bomb was heated at 120 °C for 5.5 d. The benzene was removed in vacuo to give a pink residue. The residue was purified by column chromatography over silica gel using 2:1 hexanes:EtOAc as the eluent. The desired product (RF = 0.69) was isolated as a light brown oil (0.212 g, 39.9 % yield). 1H NMR (C6D6): δ 3.30 (2H, d, 7 Hz, CH2), 6.48 (1H, d, 16 Hz, vy CH), 6.54 (1H, dd, 8 Hz, 5 Hz, py CH), 6.74 (1H, “d”, 8 Hz, py CH), 6.98 (1H, “t”, 8 Hz, py CH), 7.02-7.12 (6H, m, Ph CH, vy CH), 8.46 ppm (1H, d, 5 Hz, py CH). b. A 25 mL flask was charged with (2pyridyl)diethylphosphate (500 mg, 2.18 mmol). 15 mL Et2O was transferred to give a pale yellow solution. LiHMDS (383 mg, 2.29 mmol) was added, resulting in a color change to bright yellow. A solution of phenylacetaldehyde (262 mg, 2.18 mmol) in 4 mL Et2O was added dropwise, resulting in the formation of a white precipitate. The mixture was stirred for 12 h, then filtered through Celite. The solution was concentrated and the residue purified by column chromatography over silica gel with 3:1 hexanes:EtOAc as eluent to afford pyphp as a yellow oil devoid of impurities (262 mg, 61.5 % yield). The spectra were identical to those obtained using method a. 8. Reaction of pyphp with cis-Me2Fe(PMe3)4. To a solution of pyphp (10 mg, 0.051 mmol) in C6D6 (0.5 mL) was added cis-Me2Fe(PMe3)4 (20 mg, 0.051 mmol), resulting in a purple solution. 31P NMR (C6D6): δ -62.55 ppm (free PMe3), 2.64 (t, 35 Hz), 16.52 (d, 35 Hz), 17.84 (s), 19.27 (br d, 54 Hz), 23.51 (br d, 54 Hz), 120 25.13 ppm (br s). 9. trans-2-(2,6-dimethylphenyl)-2-vinylpyridine, dmpvp. A 25 mL flask was charged with (2-pyridyl)diethylphosphate (500 mg, 2.18 mmol). 10 mL Et2O was transferred to the flask, resulting in a pale yellow solution. LiHMDS (383 mg, 2.29 mmol) was added to give a bright yellow solution. A solution of 2,6dimethylbenzaldehyde (294 mg, 2.19 mmol) in 5 mL Et2O was added dropwise under Ar, resulting in a yellow solution with white solid. The mixture was stirred at 23 °C for 12 h, then filtered and stripped. The excess (2-pyridyl)diethylphosphate was distilled off to afford pure product as a yellow oil. 1H NMR (CDCl3): δ 2.41 (6H, s, Me), 6.71 (1H, d, 16 Hz, vy CH), 7.09 (3H, m, Ph CH), 7.17 (1H, ddd, 7.5 Hz, 5 Hz, 1 Hz, py CH), 7.37 (1H, d, 8 Hz, py CH), 7.67 (1H, dd, 7.5 Hz, 6 Hz, py CH), 7.67 (1H, d, 16 Hz, vy CH), 8.63 ppm (1H, d, 5 Hz, py CH). 10. (2,6-dimethylbenzylidene)-2-pyridylamine, dmbpaH2. A 25 mL flask was charged with 2-aminopyridine (350 mg, 3.72 mmol), 2,6-dimethylbenzaldehyde (499 mg, 3.72 mmol), CH2Cl2 (6 mL), and 4Å molecular sieves. The mixture was stirred under Ar for 4 d, then filtered and stripped to a yellow oil. 1H NMR (C6D6): δ 2.55 (6H, s, Me), 6.62 (1H, ddd, 7 Hz, 5 Hz, 1 Hz, py CH), 6.89 (2H, d, 7.5 Hz, Ph CH), 7.00 (1H, dd, 8 Hz, 7 Hz, Ph CH), 7.13 (1H, td, 8 Hz, 2 Hz, py CH), 7.24 (1H, dt, 8 Hz, 1 Hz, py CH), 8.40 (1H, ddd, 5 Hz, 2 Hz, 1 Hz, py CH), 9.91 ppm (1H, s, Im CH). 11. (2,6-dimethylbenzylidene)-2-(6-methylpyridyl)amine, dmbmpaH2. A 25 mL flask was charged with 2-amino-6-methylpyridine (409 mg, 3.78 mmol), 2,6dimethylbenzaldehyde (508 mg, 3.79 mmol), CH2Cl2 (6 mL), and 4Å molecular 121 sieves. The mixture was heated at reflux under Ar for 36 h, then filtered and stripped to give a yellow oil. 1H NMR (C6D6): δ 2.42 (3H, s, py Me), 2.55 (6H, s, Ph Me), 6.60 (1H, m, py CH), 6.90 (2H, d, 7.5 Hz, Ph CH), 7.01 (1H, d, 8 Hz, 7 Hz, Ph CH), 7.14 (2H, m, py CH), 9.87 ppm (1H, s, Im CH). 12. (dmbpa)Fe-PMe3. A 25 mL flask was charged with dmbpaH2 (112 mg, 0.533 mmol) and cis-Me2Fe(PMe3)4 (204 mg, 0.523 mmol). Benzene (8 mL) was transferred to the flask. The mixture was warmed to 23 °C and stirred for 2 h. Solvent was removed to give a dark red residue, which was triturated once with pentane to give a dark purple solid (191 mg, 74 % yield). 1H NMR (C6D6): δ 0.56 (18H, s, PMe3), 1.17 (9H, d, 4 Hz, PMe3), 1.44 (2H, t, 8 Hz, Fe-CH2), 3.51 (3H, s, Me), 6.29 (1H, t, 6 Hz, py CH), 7.10 (1H, t, 6 Hz, Ph CH), 7.20 (1H, t, 7 Hz, py CH), 7.49 (1H, d, 7 Hz, Ph CH), 7.71 (1H, d, 8 Hz, py CH), 8.28 ppm (1H, d, 5 Hz, py CH). 31P NMR (C6D6): δ 3.41 (1P, t, 38 Hz), 17.71 ppm (2P, d, 38 Hz). 13. (dmbpa)Fe-CO. A J-Young tube was charged with a solution of (dmbpa)Fe-PMe3 in 0.5 mL C6D6. The solution was degassed, back-filled with 1 atm CO, shaken vigorously, and allowed to stand for 2 d. 1H NMR (C6D6): δ 0.80 (18H, s, PMe3), 1.96 (2H, t, 8.5 Hz, Fe-CH2), 3.32 (3H, s, Ph Me), 6.15 (1H, t, 6 Hz, py CH), 7.00 (1H, t, 7.5 Hz, Ph CH), 7.05 (1H, d, 7 Hz, Ph CH), 7.41 (1H, d, 8 Hz, Ph CH), 7.56 (1H, d, 8 Hz, py CH), 8.64 ppm (1H, d, 5.5 Hz, py CH). 31P NMR (C6D6): δ 22.36 ppm (s). IR: ν(N2) = 2051 cm-1. 14. (dmbmpa)Fe-N2. A 50 mL flask was charged with dmbmpaH2 (116 mg, 0.517 mmol) and cis-Me2Fe(PMe3)4 (200 mg, 0.513 mmol). Benzene (10 mL) was transferred to the flask, the mixture was warmed to 23 °C, and stirring was continued 122 for 12 h. The volatiles were removed in vacuo to give a dark red residue, which was triturated once with pentane to give a dark red solid (185 mg, 79 % yield). 1H NMR (C6D6): δ 0.47 (18H, s, PMe3), 1.87 (2H, t, 8 Hz, Fe-CH2), 2.57 (3H, s, Ph Me), 3.33 (3H, s, py Me), 6.32 (1H, d, 7 Hz, py CH), 7.03 (1H, t, 7 Hz, Ph CH), 7.05 (1H, d, 7 Hz, Ph CH), 7.18 (1H, m, py CH), 7.48 (1H, d, 7 Hz, Ph CH), 7.55 ppm (1H, d, 8 Hz, py CH). 31P NMR (C6D6): δ 18.45 ppm (s). IR: ν(N2) = 2051 cm-1. 15. A1-H. A 10 mL flask was charged with (dmbmpa)Fe-N2 (47 mg, 0.10 mmol). 3 mL bezene was transferred to the flask, followed by transfer of PMe3 (0.10 mmol) via a 14.5 mL gas bulb. The mixture was stirred for 2 min at 23 °C then cooled to -78 °C. The mixture was exposed to 1 atm H2, warmed to 23 °C and stirred for 12 h. The red solution was stripped to a red residue, which was triturated twice with pentane to afford the product as a red solid. 1H NMR (C6D6): δ -27.18 (1h, td, 66 Hz, 44 Hz, Fe-H), 1.04 (9H, s, PMe3), 1.21 (18H, s, PMe3), 2.08 (3H, s, py Me), 2.41 (6H, s, Ph Me), 4.22 (2H, s, Ph-CH2), 5.18 (1H, m, py CH), 5.75 (1H, m, py CH), 6.86 (1H, m, Ph CH), 6.99 (2H, m, Ph CH), 7.06 ppm (1H, m, py CH). 31P NMR (C6D6): δ 21.73 (2P, d, 55 Hz), 35.47 ppm (1P, t, 55 Hz). 123 REFERENCES (1) Whittaker, A. M.; Lalic, G. Org. Lett. 2013, 15 (5), 1112–1115. (2) Mankad, N. P.; Laitar, D. S.; Sadighi, J. P. Organometallics 2004, 23 (14), 3369–3371. (3) Andrew M Fryer. MMP Inhibitors and Methods of Use Thereof. (4) González-Gómez, Á.; Añorbe, L.; Poblador, A.; Domínguez, G.; Pérez-Castells, J. Eur. J. Org. Chem. 2008, 2008 (8), 1370–1377. (5) Li, Z.; Hong, L.; Liu, R.; Shen, J.; Zhou, X. Tetrahedron Lett. 2011, 52 (12), 1343–1347. (6) Tomioka, K.; Shioya, Y.; Nagaoka, Y.; Yamada, K. J. Org. Chem. 2001, 66 (21), 7051–7054. (7) Kusama, H.; Takaya, J.; Iwasawa, N. J. Am. Chem. Soc. 2002, 124 (39), 11592– 11593. (8) Liang, Y.-F.; Zhou, X.-F.; Tang, S.-Y.; Huang, Y.-B.; Feng, Y.-S.; Xu, H.-J. RSC Adv. 2013, 3 (21), 7739–7742. (9) Hamasaka, G.; Sakurai, F.; Uozumi, Y. Chem. Commun. 2015, 51 (18), 3886– 3888. 124 Appendix 2 Synthesis and Attempted Water Oxidation Reactivity of Dihydroxy- and Tetrahydroxysalen Ligands and the Corresponding Manganese(III) Complexes Introduction In our brief efforts to develop a water oxidation catalyst, we targeted transition metal complexes with ligands that could serve the dual roles of redox activity and secondary coordination sphere hydrogen bonding. These specifications were designed to limit metal oxidation state changes and to serve as a means of organizing water molecules to facilitate the necessary O-O bond formation. The ligand framework that we chose as a starting point was the well-known salen ligand, varients of which have been used extensively for transition metal and main group metal catalysis.1,2 This ligand framework can be readily synthesized by condensation of ethylenediamine and salicylaldehyde (Eq. A2.1). Our modification was to use salicylaldehydes with additional hydroxyl groups in order to form a redoxactive catechol moiety. Oxidation of the redox-active catechol would generate a semiquinone (one-electron oxidation) or a quinone (two-electron oxidation). The goal was for the resulting quinone units to bind water and abstract hydrogen atoms in order to produce dioxygen. For example, four electron oxidation of a dihydroxysalen 125 (DHsalen) transition metal complex would give a dicationic bis(quinone) complex. Binding of two water molecules and subsequent hydrogen atom abstraction by the quinones would lead to oxygen production, as shown in Scheme A2.1. Scheme A2.1. Proposal for water oxidation with dihydroxysalen (DHsalen) complexes. Results and Discussion A2.1. Synthesis of Dihydroxysalen and Tetrahydroxysalen Metal Complexes The synthesis of dihydroxysalen, DHsalenH2, was carried out according to literature procedure.3 A mixture of ethylenediamine and 2 equiv. 2,3dihydroxybenzaldehyde was heated at reflux in toluene to afford DHsalenH2 as an orange solid in 96 % yield (Eq. A2.2). The synthesis of tetrahydroxysalen, THsalenH2, had to be carried out under Ar 126 to prevent byproduct formation. Ethylenediamine was added to a solution of 2 equiv. 2,3,4-trihydroxybenzaldehyde in MeOH at 23 °C to afford THsalenH2 as a yellow solid in 84 % yield (Eq. A2.3). With these ligands in hand, we targeted metalation with manganese to give analogs of the well-known Mn(III) salen complexes, which have been used extensively in catalysis, especially for epoxidation chemistry. Following the procedure for the synthesis of salen manganese(III) chloride complexes, a mixture of Mn(OAc)2·4H2O, DHsalenH2, and LiCl was heated at reflux in ethanol under air to afford Mn(DHsalen)Cl as a brown solid. The same protocol was followed with THsalenH2 to give Mn(THsalen)Cl as a brown solid. 127 A2.2. Catalytic Water Oxidation Attempts with Hydroxysalen Compounds Efforts towards catalytic water oxidation with hydroxysalen compounds were initially promising. Hydroxysalen compounds were dissolved in a mixture of water and DMSO for ease of solubility. Ceric ammonium nitrate, (NH4)2Ce(NO3)6, was chosen as a sacrificial oxidant due to the large positive reduction potential of the CeIV/III couple (+0.88 V vs. Fc+/Fc in H2O). When a large excess of (NH4)2Ce(NO3)6 was added to a solution of either Mn(DHsalen)Cl or Mn(THsalen)Cl in H2O/DMSO, vigorous bubbling was immediately observable. Curiously, the same result was observed for the reaction of (NH4)2Ce(NO3)6 with THsalenH2, showing that manganese is not necessary for the reaction to occur. The reactions of excess (NH4)2Ce(NO3)6 with THsalenH2 and Mn(THsalen)Cl in H2O/DMSO were repeated, only with degassing prior to addition of (NH4)2Ce(NO3)6. The amount of gas produced was measured by using a Toepler pump. For THsalenH2, there were 0.19 mol of gas produced per mol of (NH4)2Ce(NO3)6 (Eq. A2.6), whereas Mn(THsalen)Cl gave 0.21 mol of gas per mol of oxidant under the same conditions (Eq. A2.7). To probe the role of the extra hydroxyl groups on the catalysis, the same procedure was repeated with Mn(salen)Cl (Eq. A2.8). Surprisingly, the production of gas was again observed, albeit in lesser 128 quantities (0.12 mol of gas per mol of oxidant). Giving the puzzling results above, the identity of the gas produced with assayed by GC-MS. Notably, there was no increase in oxygen observed relative to the control experiment. However, there was a new peak (m/z = 43.99) not present in the control. Due to the resolution of the instrument, a definitive assignment could not be made. The two obvious candidates are CO2 (expected m/z = 44.0095) and N2O (expected m/z = 44.0128). It is chemically unlikely that CO2 is produced in the reaction, as it would require the oxidation of the ligand framework to CO2. That leaves N2O as the likely identity of the gas. One possible route for the formation of N2O is the catalytic decomposition of ammonium nitrate, NH4NO3. This reaction is easily achieved by heating solid NH4NO3 above its melting point, 170 °C. It is worth noting that the conversion of 129 NH4NO3(aq) to N2O and 2 equiv. H2O is highly exergonic, with a calculated ΔG°rxn of -43.0 kcal/mol (Eq. A2.9). The mechanism of the catalysis by these salen compounds is unclear, as is the role of the oxidant, since the conversion of NH4NO3 to N2O is not accompanied by a net redox change. Experimental General Considerations. All manipulations were performed using either glovebox or high vacuum line techniques. All glassware was oven dried. THF and ether were distilled under nitrogen from purple sodium benzophenone ketyl and vacuum transferred from the same prior to use. Hydrocarbon solvents were treated in the same manner with the addition of 1-2 mL/L tetraglyme. Benzene-d6 and was dried over sodium, vacuum transferred and stored over sodium. THF-d8 was dried over sodium and vacuum transferred from sodium benzophenone ketyl prior to use. All chemicals were commercially available and used as received. NMR spectra were obtained using an INOVA 400 MHz and 500 MHz spectrometers. Chemical shifts are reported relative to DMSO-d6 (1H δ 2.50; 13C{1H} δ 39.52). Procedures. 1. Dihydroxysalen, DHsalenH2. Ethylenediamine (0.45 mL, 6.7 mmol) was added to a 250 mL flask containing a suspension of 2,3-dihydroxybenzaldehyde (1.90 g, 13.8 mmol) in 150 mL toluene. The flask was equipped with a Dean-Stark trap and heated at reflux for 3 h, resulting in an orange precipitate. The mixture was cooled to 130 23 °C, filtered, and washed with Et2O (3 x 15 mL) to give the product as an orange solid (1.93 g, 96 % yield). 1H NMR (DMSO-d6): δ 3.93 (4H, s, N-CH2CH2N), 6.65 (2H, t, 8 Hz, Ph CH), 6.82 (2H, dd, 8 Hz, 2 Hz, Ph CH), 6.85 (2H, dd, 8 Hz, 2 Hz, Ph CH), 8.54 ppm (2H, s, N=CH). 2. Tetrahydroxysalen, THsalenH2. Under Ar, ethylenediamine (0.32 mL, 4.8 mmol) was added to a light brown solution of 2,3,4-dihydroxybenzaldehyde (1.48 g, 9.58 mmol) in 50 mL MeOH, resulting in the formation of a yellow precipitate. After stirring at 23 °C for 4 h, the mixture was filtered and the precipitate washed with Et2O (4 x 15 mL) to afford the product as a fine yellow powder (1.34 g, 84 % yield). 1H NMR (DMSO-d6): δ 3.81 (4H, s, NCH2CH2N), 6.23 (2H, d, 8 Hz, Ph CH), 6.66 (2H, d, 8 Hz, Ph CH), 8.33 ppm (2H, s, N=CH). 3. Dihydroxysalen manganese(III) chloride, Mn(DHsalen)Cl. A 50 mL flask was charged with DHsalenH2 (300 mg, 0.999 mmol), Mn(OAc)2·4H2O (492 mg, 2.01 mmol), and 25 mL EtOH. The mixture was heated at reflux for 1 h, then cooled to 23 °C. LiCl (160 mg, 3.77 mmol) was added and the mixture was heated at reflux for 30 min. The mixture was cooled to 0 °C, filtered, and washed with Et2O to give a dark brown solid (204 mg, 52.5 % yield). 4. Tetrahydroxysalen manganese(III) chloride, Mn(THsalen)Cl. A 50 mL flask was charged with THsalenH2 (300 mg, 0.903 mmol), Mn(OAc)2·4H2O (443 mg, 1.81 mmol), and EtOH (25 mL). The mixture was heated at reflux for 1 h, then cooled to 23 °C. LiCl (145 mg, 3.42 mmol) was added and the mixture was heated at reflux for 30 min. The mixture was cooled to 0 °C, filtered, and washed with Et2O to give a brown solid (250 mg, 65.8 % yield). 131 REFERENCES (1) Cozzi, P. G. Chem. Soc. Rev. 2004, 33 (7), 410–421. (2) Zhang, W.; Loebach, J. L.; Wilson, S. R.; Jacobsen, E. N. J. Am. Chem. Soc. 1990, 112 (7), 2801–2803. (3) Vezin, H.; Lamour, E.; Routier, S.; Villain, F.; Bailly, C.; Bernier, J.-L.; Catteau, J. P. J. Inorg. Biochem. 2002, 92 (3–4), 177–182. 132