Structure And Reactivity Of O-Lithiated Species: Spectroscopic And Computational Investigations Of Solution Structure And Reaction Mechanism

Abstract

Solution structural characterization of organolithium aggregates has been advanced through the efforts of Collum and coworkers. These characterizations necessarily precede detailed mechanistic studies, and may guide the engineering of new aggregates of interest. Amino alkoxides used as chiral auxiliaries by Merck and DuPont have been characterized through the use of the method of continuous variations at high temperatures. The results are corroborated by low temperature NMR data, X-ray structures, and DFT computations. Chiral mixed aggregates of lithium hexamethyldisilazide and amino alkoxides of potential synthetic utility were discovered in the course of this work, and their structure elucidated through a new extension of the Method of Continuous Variations. In an effort to extend the utility of amino alkoxides as chiral auxiliaries, mixtures of achiral enolates and phenolates with amino alkoxides were explored. A detailed mechanistic study of an aza aldol addition is presented in Chapter II herein. Following structural studies, detailed mechanistic studies are performed to understand the origins of product ratios, and correlations between rate and reaction conditions that are necessary for optimization. This mechanistic study is presented in the context of previous assumptions about the aggregation dynamics along the reaction coordinate, and is the first mechanistic study of an aza aldol addition. The dimer-based reaction was uncloaked through the use of in-situ ReactIR, rapid inject NMR, and DFT computations.