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 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 or the δ 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 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.