Enantioselective Synthesis of Axially Chiral Alkylidenecycloalkanes via Copper-Catalyzed Functionalization of Acyl Allenols

Axially
chiral alkylidenecycloalkanes are an important
type of
stereoisomer, resulting from the perpendicular arrangement of two
pairs of substituents. Despite the considerable progress made in the
catalytically enantioselective synthesis of atropisomers, the available
methods for accessing axially chiral alkylidenecycloalkanes have been
underutilized. In this study, we describe a copper-catalyzed enantioselective
synthesis of axially chiral alkylidenecycloalkanes using acyl allenols.
The axial chirality is established through a central to axial transfer
via an enantioenriched allylcopper species. This reaction features
mild conditions, >30:1 regioselectivities, and up to 98% ee. Control
experiments reveal that the bulky size of the leaving group has a
significant influence on the enantioselectivity of the reaction. The
alkene and vinylboronate groups of the products provide versatile
platforms for further transformations to enrich the structural diversity
of products.