NHC‐Organocatalyzed C_Ar−O Bond Cleavage: Mild Access to 2‐Hydroxybenzophenones

Abstract

A Truce-Smiles rearrangement of acyl-anion equivalents generated by N-heterocyclic carbene (NHC) catalysis has been achieved. The developed method includes C_Ar -O, C_Ar -S, or C_Ar -N bond cleavage for the formation of a C_Ar -C bond and enables access to 2-hydroxybenzophenones, an important structural motif that is present in several bioactive natural products. By utilizing this procedure, the alkaloid taxilamine was synthesized in three steps. DFT calculations and control experiments support a classical S_N Ar mechanism with a catalyst-bound Meisenheimer-type intermediate. The method features mild reaction conditions, excellent functional-group tolerance, and a broad substrate scope, including various classes of (hetero)arenes.