B(MIDA)-directed site-selective intermolecular halofluoroalkylation of alkenes: synthesis of diversely functionalized building blocks

Abstract

α-Halo borides are generally constructed via Matteson homologation, and the synthesis of both fluorinated and functionalized ambiphilic boronates is challenging and has received inadequate attention. Herein, we describe the N-methyliminodiacetyl boronate [B(MIDA)]-directed halogenation of alkenes via a complementary sequence involving fluoroalkyl radical addition followed by guided radical-to-metal oxidative addition and C–X reductive elimination. The alkali cation and functional groups in B(MIDA) enable coulombic interaction and weak attraction with halogens, which could weaken the Pd–X bond and assist in C–X bond formation and is verified by DFT calculations. As a result, a wide variety of highly functionalized fluorinated α-halo boronates, including drugs and natural products, are obtained in good or moderate yields through the unique catalytic manifold. Notably, the trifunctionalized (F, X, B) building block could be transformed into diverse modified fluorinated products.