Pseudoephenamine: A Practical Chiral Auixiliary for Asymmetric Synthesis

Abstract

Pseudoephedrine has been used as a chiral auxiliary in diastereoselective alkylation reactions, providing easy access to enantiomerically enriched carboxylic acids, alcohols, ketones, and aldehydes. Because pseudoephedrine can be transformed into methamphetamine and other illegal drugs, many countries restrict or ban its sale and distribution, which can complicate its use in academic and industrial settings. This thesis shows that (1S,2S)-2-methylamino-1,2-diphenylethanol and (1R,2R)-2-methylamino-1,2- diphenylethanol (synonymously, (1S,2S)- and (1R,2R)-pseudoephenamine 30, respectively) enable a broad range of utilities in asymmetric synthesis that meet or exceed those that previously characterized the pseudoephedrine system alone, with several advantages. First, these auxiliaries are free from regulatory restrictions and are not known to be transformable into illegal substances; second, asymmetric alkylation reactions that employ pseudoephenamine as a chiral auxiliary proceed with equal or greater diastereoselectivities than the corresponding reactions employing pseudoephedrine, with notable improvements in the selectivities of the alkylation reactions that form quaternary carbon stereocenters; and lastly, amides derived from pseudoephenamine exhibit a greater propensity to be crystalline compounds than the corresponding pseudoephedrine derivatives.