Phosphine-Catalyzed Doubly Stereoconvergent γ-Additions of Racemic Heterocycles to Racemic Allenoates: The Catalytic Enantioselective Synthesis of Protected α,α-Disubstituted α-Amino Acid Derivatives

Methods have recently been developed for the phosphine-catalyzed asymmetric gamma-addition of nucleophiles to readily available allenoates and alkynoates to generate useful alpha,beta-unsaturated carbonyl compounds that bear a stereogenic center in either the gamma or the delta position (but not both) with high stereoselectivity. The utility of this approach would be enhanced considerably if the stereochemistry at both termini of the new bond could be controlled effectively. In this report, we describe the achievement of this objective, specifically, that a chiral phosphepine can catalyze the stereoconvergent gamma-addition of a racemic nucleophile to a racemic electrophile; through the choice of an appropriate heterocycle as the nucleophilic partner, this new method enables the synthesis of protected alpha,alpha-disubstituted alpha-amino acid derivatives in good yield, diastereoselectivity, and enantioselectivity.