Construction of All-Aliphatic Stereocenters via Enantioselective Alkene Hydroalkylation

Chiral carbon–carbon bond formation is a cornerstone of synthetic chemistry, enabling access to the intricate three-dimensional frameworks found in chiral natural products, pharmaceuticals, pesticides, and material molecules. Despite considerable advances, achieving high enantioselectivity in the formation of C( sp 3 )–C( sp 3 ) bonds remains particularly demanding when the reacting partners are purely aliphatic, offering minimal electronic or steric contrast for chiral catalysts to exploit. Here we show cobalt catalysis featuring an umbrella-shaped chiral pocket with multiple dispersion interactions, which constitutes a discrimination system highly sensitive to substrate steric hindrance. This system enables the precise differentiation of two alkyl substituents with similar electronic properties but different steric hindrances and facilitates the asymmetric hydroalkylation of purely aliphatic alkenes. This approach significantly enhances the manipulative capability of asymmetric carbon–carbon bond formation beyond traditional cross-coupling systems and enzymatic catalysis, potentially addressing the persistent challenge of the enantioselective construction of a chiral C( sp 3 ) center with all purely aliphatic substituents.