Catalytic Asymmetric Synthesis of Axially Chiral Methylenecyclopropanes

Abstract

Atropisomeric compounds and 1,3-disubstituted allenes are the most common examples of axial chirality in organic chemistry. However, there are less explored classes of axially chiral molecules that may also hold significant value in asymmetric synthesis. Here, we report a catalytic asymmetric synthesis of axially chiral methylenecyclopropanes by a [2 + 1]-cycloaddition of an alkene and a vinylidene equivalent. Computational models provide a rationale for the origin of asymmetric induction and indicate that key elements of stereocontrol differ from catalytic enantioselective cyclopropanation reactions using carbenes. Methylenecyclopropanes participate in a broad range of axial-to-central chirality transfer reactions that take advantage of addition to the alkene or ring-opening of the strained three-membered ring.