A general method for the asymmetric synthesis of quaternary carbons: Reductive formation and alkylation of alpha,alpha-disubstituted enolates

A new, general method for the asymmetric synthesis of quaternary carbons is described. This technique involves stereocontrolled generation of α,α-disubstituted amide enolates via reduction of bicyclic α,α-disubstituted α-thioglycolate lactams using one-electron transfer reagents. A model of the geometric constraints necessary to reductively prepare α,α-disubstituted amide enolates with control of enolate E/Z stereochemistry is described and several chiral auxiliaries were prepared to test this design.; Successful preparation, trapping, isolation and characterization of α,α-disubstituted amide enolates is described. This reductive enolization method allows, for the first time, the stereoselective preparation of both E- and Z-acyclic α,α-disubstituted amide enolates.; Reactivity and selectivity of α,α-disubstituted amide enolates in alkylation with alkyl halides is explored. Dichotomous reactivity is observed for both E- and Z-α,α-disubstituted amide enolates. Z-α,α-Disubstituted amide enolates are shown to alkylate with high levels of stereoselectivity; E-α,α-disubstituted amide enolates alkylate with poor stereoselectivity.; Methods for isolation of the quaternary carbon-containing adducts are described. Conditions for the determination of the enantiomeric excess of chiral, non-racemic neopentyl alcohols were developed and are also described.; Development of a facile, environmentally friendly, modular synthesis of a model second-generation chiral auxiliary using simple, inexpensive starting materials is described.