DILITHIUM AND DISODIUM SALTS OF PSEUDOEPHEDRINE-DERIVED MYERS ENOLATES: STEREOSELECTIVITY AND MECHANISM OF ALKYLATION
The structures and reactivities of pseudoephedrine-derived dianionic Myers enolates are examined. A combination of NMR and IR spectroscopic, crystallographic, and computational data reveal that the homoaggregated dianions form octalithiated tetramers displaying S4-symmetric Li8O8 cores and overall C2 symmetry. Computational and isotopic labeling studies reveal strong N–Li contacts in the carboxamide enolate moiety. The method of continuous variations proves deceptive, as octalithiated tetrameric homoaggregates afford hexalithiated trimeric heteroaggregates. A lithium diisopropylamide–lithium enolate mixed aggregate is found to be a C2-symmetric hexalithiated species incorporating two enolate dianions and two lithium diisopropylamide (LDA) subunits. Structural and rate studies show that lithium chloride has little effect on the dynamics of the enolate homoaggregates but forms adducts of unknown structure. Rate studies of alkylations indicate that the aging of the aggregates can have effects spanning orders of magnitude. The LiCl–enolate adduct dramatically accelerates the reaction but requires superstoichiometric quantities owing to putative autoinhibition. Efforts and progress toward eliminating the requisite large excess of LiCl are discussed. Pseudoephedrine-derived dianionic Myers enolates were generated using sodium diisopropylamide (NaDA) in THF solution. The reactivities and selectivities of the disodium salts largely mirror those from the dilithium salts but without requisite large excesses of inorganic salts (LiCl) or mandated dilute solutions. The disodium salts require careful control of temperature to preclude deleterious aggregate aging effects and intervening O-alkylations. Structural studies and density functional theory computations show a dominant highly symmetric octagonal prism quite unlike the lithium analog. No enolate-NaDA mixed aggregates are observed with excess NaDA. Rate studies show an alkylation mechanism involving an intervening tetramer-monomer pre-equilibrium followed by rate-limiting alkylation of tetrasolvated monomers. Deleterious aging effects on reactivity are traced to changes in aggregate structure. A crystal deriving from samples aged at ambient temperature contains six-dianionic subunits and two monoanionic (alkoxide-only) subunits that appear to correlate with reduced percent conversions of the alkylations.
Physical chemistry; Organo-lithium enolate; Organo-sodium enlate; Pseudoephedrine Derived Myers Enolate; Chemistry; Organic chemistry
Collum, David B.
Coates, Geoffrey; Fors, Brett P.
Chemistry and Chemical Biology
Ph.D., Chemistry and Chemical Biology
Doctor of Philosophy
dissertation or thesis