MeOTf-catalyzed Friedel-Crafts alkylation of benzoxazolones, benzothiazolones, indolinones and benzimidazolones with activated secondary alcohols.

Abstract

Herein, we have revealed a methodology for the selective C-alkylation of benzoxazolones, benzothiazolones, indolinones, and benzimidazolones incorporating activated alcohols catalysed by methyltrifluoromethanesulfonate (MeOTf). This method offers a green, atom-economic alternative for the synthesis of alkylated heterocycles, producing water as the only byproduct. Alcohols, due to their abundance, ease of preparation, and environmental friendliness, have become attractive alkylating agents. The developed reaction conditions demonstrate high yields and broad applicability across various N-alkylated heterocycles, highlighting the versatility of the MeOTf catalysis. The method was also adapted for one-pot consecutive N- and C-alkylation and chemoselective C-alkylation in heterocycles containing a free -NH group. This approach provides a practical and efficient route for the functionalization of bioactive heterocyclic compounds.