Catalytic Lewis Base Additive Enables Selective Copper-Catalyzed 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 that enables the transformation of O-benzoyl hydroxylamines into alpha-functionalized cyclic secondary amines by means of a copper-catalyzed regio-, stereo-, and chemoselective coupl i n g with allenes and bis(pinacolato)diboron. A key feature of the present transformation is the use of a catalytic Lewis base additive which inhibits the competing C-N bond forming reaction between the catalytically generated boron-substituted allylcopper intermediate with the O-benzoyl hydroxylamine, thus enabling in situ transformation of the latter into an alicyclic imine which undergoes selective C-C bond formation with the allylcopper species.

Automated summary

Functionalized alicyclic amines are crucial for synthesizing bioactive compounds and drugs. This study presents a novel copper-catalyzed method for transforming O-benzoyl hydroxylamines into alpha-functionalized cyclic secondary amines, using unique additives to inhibit competing reactions. The method exhibits high selectivity and efficiency.