N-Heterocyclic Carbene Catalyzed Concerted Nucleophilic Aromatic Substitution of Aryl Fluorides Bearing α,β-Unsaturated Amides

Abstract

Concerted nucleophilic aromatic substitution (CS_N Ar) has emerged as a powerful mechanistic manifold, in which nucleophilic aromatic substitution can proceed in one step without the need to form a Meisenheimer intermediate. However, all of the CS_N Ar reactions reported thus far require a stoichiometric strong base or activating reagent, and no catalytic variants have yet been reported. Herein, we report an N-heterocyclic carbene (NHC)-catalyzed intramolecular cyclization of acrylamides that contain a 2-fluorophenyl group on the nitrogen through a CS_N Ar reaction. By using this catalytic method, it is possible to synthesize an array of quinolin-2-one derivatives, which are common structural motifs in pharmaceuticals and organic materials. DFT calculations unambiguously revealed that this reaction proceeds through the concerted nucleophilic aromatic substitution of aryl fluorides, in which a stereoelectronic σ (C_ipso -C_β )→ σ*(C_ipso -F) interaction critically contributes to the stabilization of the transition state for the cyclization.

Keywords: N-heterocyclic carbenes; Organocatalysis; aryl fluorides; nucleophilic aromatic substitution; umpolung.