Construction of Acyclic Quaternary Carbon Stereocenters by Catalytic Asymmetric Hydroalkynylation of Unactivated Alkenes.

Abstract

Quaternary carbon stereocenters are common structural motifs in organic synthesis. The construction of these stereocenters in a catalytic and enantioselective manner remains a prominent synthetic challenge. In particular, methods for the synthesis of alkyne-substituted quaternary carbon stereocenters are very rare. Previous catalytic systems for hydroalkynylation of alkenes create tertiary stereocenters. We describe here an iridium catalyzed asymmetric hydroalkynylation of nonactivated trisubstituted alkene. The hydroalkynylation of β,γ-unsaturated amides occurs with high regio- and enantioselectivities to afford alkyne-substituted acyclic quaternary carbon stereocenters. Computational and experimental data suggest that the enantioselectivity is not only determined by the facial selectivity of the alkene but also by an alkene isomerization process. This strategy provides an efficient method to access alkyne-substituted acyclic quaternary carbon stereocenters with minimally functionalized starting materials.