Copper- and DMF-mediated switchable oxidative C–H cyanation and formylation of imidazo[1,2-a]pyridines using ammonium iodide?

Organic & Biomolecular Chemistry Pub Date: 2020-10-22 DOI: 10.1039/D0OB01838D

Abstract

The cyanation and formylation of imidazo[1,2-a]pyridines were developed under copper-mediated oxidative conditions using ammonium iodide and DMF as a nontoxic combined cyano-group source and DMF as a formylation reagent. Mechanistic studies indicate that the cyanation of imidazo[1,2-a]pyridines proceeds through a two-step sequence: initial iodination and then cyanation. The cyanation has a broad substrate scope and high functional group tolerance, and can be safely conducted on a gram scale. A novel copper-mediated formylation using the widely available DMF as the formylation reagent and environmentally friendly molecular oxygen as the oxidant has also been developed. This protocol also provided a convenient approach for the synthesis of clinically used saripidem.

Graphical abstract: Copper- and DMF-mediated switchable oxidative C–H cyanation and formylation of imidazo[1,2-a]pyridines using ammonium iodide
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