Cobalt-catalyzed asymmetric three-component reductive addition of alkynes with alkyl halides and imines

The catalytic dicarbofunctionalization of alkynes is a highly efficient strategy for the rapid assembly of complex, multi-substituted acyclic alkenes from simple feedstocks. Despite significant progress having been made in various racemic transformations, the direct enantioselective construction of multi-substituted acyclic alkenes bearing sterically congested tetrasubstituted stereocenters via multicomponent radical pathways remains a formidable and unsolved challenge in organic chemistry. Herein, we report a cobalt-catalyzed asymmetric three-component radical addition of terminal alkynes, ketimines, and unactivated alkyl iodides, which efficiently delivers polysubstituted allylamine derivatives featuring challenging tetrasubstituted stereocenters. This enantioselective addition protocol proceeds under mild reductive conditions and exhibits broad substrate scope with high functional group tolerance, delivering products with excellent stereoselectivity. Preliminary mechanistic investigations suggest a radical-based cascade process involving stereospecific alkyl radical addition to the alkyne followed by stereoselective addition to the ketimine. This work provides a straightforward and modular strategy to access highly functionalized chiral allylic amines from readily available starting materials. The authors report a cobalt-catalyzed asymmetric three-component radical addition of terminal alkynes, ketimines, and unactivated alkyl iodides, which efficiently delivers polysubstituted allylamine derivatives featuring challenging tetrasubstituted stereocenters.