Asymmetric nickel-catalyzed three-component assembly of allylic amines from alkynes, imines and organoboron reagents

Abstract

[Image] ... Allylic amines are assembled in one step from alkynes, imines, and organoboron reagents (boronic acids or boranes) using a catalyst derived from Ni(cod)2 and (c-CsH9)3P or (o-anisyl)3P. This catalytic, three-component process is tolerant of ketones, esters, and free hydroxyl groups; a degree of functional group compatibility unusual for imine addition reactions. The mode of addition across the alkyne is exclusively cis (>97:3), thereby establishing the alkene geometry of the product in the course of two carbon-carbon bond forming events. Even though nickel- catalyzed multi-component coupling reactions involving additions to carbonyl compounds have been reported, the process described herein is the first such example involving imines and also the first that utilizes boronic acids. [Image] ... An enantioselective catalytic version of the above reaction is developed to provide enantiomerically enriched, tetrasubstituted allylic amines in a single operation. Using the complex derived from Ni(cod)2 and a P-chiral ferrocenyl phosphine A, both aliphatic and aromatic alkynes and imines undergo coupling reactions in high yields (up to 95%) and enantioselectivities (up to 89%). A (tert-butyldimethyl)silyloxyethyl (TBSOCH2CH2-) group on the imine nitrogen not only maximizes reactivity and selectivity in these transformations, but is also easily removed after the coupling reaction providing direct access to versatile primary allylic amines that can be recrystallized to optical purity.