Cascade Reaction of Isocyanides with Carboxylic Acid and CD3SSO3Na: Toward S-CD3 Thiocarbamates

We developed an unprecedented cascade reaction involving isocyanides with carboxylic acids and CD₃SSO₃Na to access S-CD₃ thiocarbamates with the formation of two C-N bonds and one C-S bond. Preliminary mechanistic investigations disclose that these three-component reactions precede the esterification of carboxylic acids with isocyanides, generating a capable N-alkyl-N-formyl amide followed by thiolation with CD₃SSO₃Na to provide the corresponding products. The transformation has outstanding features in mild reaction conditions, effortless experimental operation, structural modification of polyfunctional carboxylic acid drugs, and large-scale preparation.