Regiospecific α-arylation of diverse carbonyl compounds using an organobismuth transporter

Abstract

The α-arylation of carbonyl compounds is a cornerstone transformation in the synthesis of pharmaceuticals and natural products. Despite decades of effort using transition metal, main-group, and photoredox strategies, a general and practical α-arylation method with broad substrate scope has remained elusive. Here we show that 9-bismatriptycene (BisTrip), a rigid, shackled form of triphenylbismuth, functions as a universal aryl group transporter, enabling controlled and regiospecific α-arylation of diverse ketones, enabling the formation of sterically demanding quaternary centers and incorporation of iodoaryl units. BisTrip is readily loaded with aryl groups by a one-pot procedure using arylboronic acids to give Aryl-BisTrip and, after transferring the aryl to the enolate, is recovered quantitatively. Arylation of lithium enolates proceeds within seconds even at −78 °C and shows high fidelity in a memory-of-chirality experiment. Computations support a low barrier for C–C bond formation and account for the observed axial selectivity, establishing BisTrip as a practical platform for α-arylation.