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 ap owerful mechanistic manifold, in which nucleophilic aromatic substitution can proceed in one step without the need to form aM eisenheimer intermediate. However,a ll of the CS N Ar reactions reported thus far require as toichiometric 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 a2-fluorophenyl group on the nitrogen through aCS N Ar reaction. By using this catalytic method, it is possible to synthesizeanarrayofquinolin-2-one derivatives,w hich are common structural motifs in pharmaceuticals and organic materials.D FT calculations unambiguously revealed that this reaction proceeds through the concerted nucleophilic aromatic substitution of aryl fluorides,i n which as tereoelectronic s (C ipso -C b )! s*(C ipso -F) interaction critically contributes to the stabilization of the transition state for the cyclization. Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.1002/anie.201907837. Scheme 1. S N Ar and CS N Ar reactions. Angewandte Chemie Zuschriften Scheme 3. DFT calculations. a) Energy diagram for the cyclization reaction of 1a with L6.b )HOMO orbitals in TS and the NICS(0) values of Int 1 and TS.c)Charge distribution in TS based on NBO analysis. d) s (C ipso ÀC b )b onding orbital from NBO analysis. e) s*( C ipso ÀF) antibonding orbital from NBO analysis. f) Comparison of the nucleophilicity of the simplified ylide intermediate Int3 with different NHC catalysts based on the HOMO energy levels.