Nickel-Catalyzed Enantioselective Construction of Axially Chiral B-N Embedded Seven-Membered Bridged Biaryls via Trifunctionalization of Terminal Alkynes

Abstract

We report a nickel-catalyzed enantioselective construction of axially chiral seven-membered bridged biaryls via sequential borylation and trans-addition of terminal alkynes. This trifunctionalization method features a one-pot procedure starting from readily available terminal alkynes and heterobiaryl electrophiles. The transformation proceeds under mild conditions, affording up to 98% yield and up to 98% ee, and accommodates a broad range of aryl and alkyl alkynes, heterobiaryl bromides and triflates, as well as various triarylborane migrating groups. Notably, this reaction enables the catalytic asymmetric construction of structurally rigid seven-membered bridged biaryl scaffolds, a class of chiral organoboron compounds that remain challenging to synthesize via established methods. Mechanistic studies, including nitrogen-directing group experiments, radical trapping, time-course monitoring, and nonlinear effect analysis, support a trans-addition pathway followed by intramolecular boron capture by a proximal nitrogen atom. The synthetic utility is further demonstrated by gram-scale reactions, late-stage diversification of natural product–derived alkynes, and product transformations.