Lewis Base Promoted Delayed Copper Catalysis: Borylative α-C-H Allylation of Alicyclic Amines

Functionalized alicyclic amines are important building blocks for the synthesis of bioactive natural compounds and drugs. Existing methods of functionalization are typically limited to the synthesis of protected amines or the use of highly basic organometallic reagents that can compromise functional group tolerance. Here, we report a novel approach for the synthesis of α-functionalized cyclic secondary amines. The method employs a copper/bisphosphine catalyst which promotes a regio-, stereo- and chemoselective coupling between allenes, bis(pinacolato)diboron and O-benzoyl hydroxylamines that involves trapping of an in-situ generated alicyclic imine by a catalytic boron-substituted allylcopper intermediate. Successful implementation requires that competing reaction between the allylcopper complex and hydroxylamine is suppressed while imine is formed. This challenge was met by using a catalytic amount of Lewis base additive which delays the catalyst function towards C-N coupling thus enabling selective C-C coupling.