Chemoselective Dual Functionalization of Phenols via Relay Catalysis of Borane with Different Forms

Abstract

A highly efficient and chemoselective dual functionalization of unprotected phenols with αor βhydroxyl acids is presented. A variety of valuable benzofuranones and dihydrocoumarins are delivered in moderate to high yields. Density functional theory (DFT) calculations and control experiments indicate that an untypical Friedel-Crafts alkylation and the subsequent lactonization are catalyzed by the Lewis acid form and the Brønsted acid form of borane, respectively. Gram-scale experiments and late-stage functionalization of complex molecules have been performed to highlight the utility of this reaction.

Dynamic hydrogen bonds promote C–H functionalization driven by Cl− anion

“…More inspections of the simulated structures indicate that 42 out of 50 trajectories (84%) in trajectory C at the solvation model without additive led to form enolate intermediates with the O1⋯H-O2 hydrogen bond, while 8 out of 12 trajectories forming O2-H⋯Cl hydrogen bond became dominant with 67% distribution under the additive Me 4 NCl condition. We thus speculate the O2-H⋯Cl interaction as a linker of two fragments may inhibit the Rh species dissociation that could also be verified by time [42,43]. This proton source assisted mechanism was in agreement with the metal carbenoid O-H insertion [9,10].…”

Nickel/Brønsted acid dual-catalyzed regioselective C–H bond allylation of phenols with 1,3-dienes

“…1a), the direct and selective transformation of simple phenols has attracted extensive interest. 7 However, the ambident nucleophilic nature of phenols makes their site-selective functionalization a significant challenge. 8 In particular, the alkylation of phenols suffers from O- vs. C-selectivity (Fig.…”

Hydrogen bonds promote site-selective phenol functionalization enabled by Cl- anion

“…We suspected that in the pathway there was a possibility that hydrogen bond interaction may control the the dual roles. 50,51 This proton source assisted mechanism was in agreement with the metal carbenoid O-H insertion. 11,12 The 1,2-oxidative addition might be the second potential pathway with 23.8 kcal/mol activation barrier.…”