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

Abstract

Concerted nucleophilic aromatic substitution (CSNAr) 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 CSNAr reactions reported thus far require a stoichiometric strong base or activating reagent and no catalytic variants have yet been reported. Herein, we report on the N-heterocyclic carbene (NHC)-catalyzed intramolecular cyclization of acrylamides that contain a 2-fluorophenyl group on the nitrogen via a CSNAr reaction. Using this catalytic protocol, it is possible to synthesize an array of quinolin-2-one derivatives, which are common structural motifs found 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 sigma (Cipso-Cβ) → sigma* (Cipso-F) interaction critically contributes to the stabilization of the transition state for this cyclization.