Catalyst- and Reagent-Free Formal Aza-Wacker Cyclizations Enabled by Continuous-Flow Electrochemistry

Angew Chem Int Ed Engl. 2021 May 10;60(20):11237-11241. doi: 10.1002/anie.202101835. Epub 2021 Apr 7.

Abstract

The development of efficient and sustainable methods to access saturated N-heterocycles is of great importance because of the prevalence of these structures in natural products and bioactive compounds. Pd-catalyzed aza-Wacker type cyclization is a powerful method and provides access to N-heterocycles bearing an alkene moiety available for further synthetic manipulations from readily available materials. Herein we disclose a catalyst- and reagent-free formal aza-Wacker type cyclization reaction for the synthesis of functionalized saturated N-heterocycles. Key to the success is to conduct the reactions in a continuous-flow electrochemical reactor without adding supporting electrolyte or additives. The reactions are characterized by broad tolerance of di-, tri- and tetrasubstituted alkenes.

Keywords: continuous flow; cyclization; electrochemistry; heterocycles; radical reactions.

Publication types

  • Research Support, Non-U.S. Gov't