TosMIC as a powerful reagent for site-selective α-formamidomethylation of α-enolic dithioesters

Herein, we describe a metal-free facile method for the direct synthesis of α-formamidoalkyl-β-ketodithioesters by employing easily accessible α-enolic dithioesters (EDTEs) and p-tosylmethyl isocyanide (TosMIC) via base-mediated cross-detosylative C–C coupling under an open atmosphere. This protocol is mild, operationally simple, highly efficient, and easy to get highly functionalized products in good-to-high yields. A simple mechanism involving Cs2CO3 that promotes highly selective nucleophilic attack of the α-carbon of EDTE to TosMIC followed by hydrolysis is proposed. This efficient approach opens up a new avenue for exploring the synthesis of multifunctional molecules. The carbonyl, dithioester, and amide groups of the products offer a platform for late-stage modification, which could rapidly enrich the structural diversity of the products.