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DOI: 10.1055/a-2655-5237
TosMIC as a Powerful Reagent for Site-Selective α-Formamidomethylation of α-Enolic Dithioesters
Funding Information We gratefully acknowledge the financial support from the Anusandhan National Research Foundation, ANRF (CRG/2023/000021); the IoE Incentive grant, BHU (Scheme No. 6031); and the JC Bose National Fellowship (JCB/2020/000023), New Delhi.
Dedication
Dedicated to Prof. H. Ila on her 80th birthday.
Abstract
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.
Publication History
Received: 31 May 2025
Accepted after revision: 15 July 2025
Accepted Manuscript online:
15 July 2025
Article published online:
20 August 2025
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