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

2015-12-17T08:51:21Z (GMT) by Marcin Kalek Gregory C. Fu
Methods have recently been developed for the phosphine-catalyzed asymmetric γ-addition of nucleophiles to readily available allenoates and alkynoates to generate useful α,β-unsaturated carbonyl compounds that bear a stereogenic center in either the γ <i>or</i> the δ position (but not both) with high stereoselectivity. The utility of this approach would be enhanced considerably if the stereochemistry at <i>both</i> 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 γ-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 α,α-disubstituted α-amino acid derivatives in good yield, diastereoselectivity, and enantioselectivity.