Enantioselective Synthesis of α-Chiral Bicyclo[1.1.1]pentanes via Multicomponent Asymmetric Allylic Alkylation

Bicyclo[1.1.1]pentanes (BCPs) have emerged as important structural motifs in drug design. However, asymmetric transformations that provide chiral BCPs bearing an adjacent stereocenter are still scarce. Here, we report a catalytic methodology for the enantioselective synthesis of α-chiral 1,3-difunctionalized BCPs from a three-component coupling of [1.1.1]propellane, a Grignard reagent, and an allylic phosphate. The reaction proceeds via the addition of the Grignard reagent to [1.1.1]propellane followed by an asymmetric N-heterocyclic carbene (NHC)-catalyzed allylic substitution of the resulting BCP-Grignard, providing a broad range of α-chiral BCPs with excellent levels of regioselectivity and enantioselectivity.