One-Pot Syntheses of Substituted Oxazoles and Imidazoles from the Isocyanide Asmic

Substituted oxazoles and imidazoles are synthesized in one pot from the isocyanide building block Asmic (anisylsulfanylmethyl isocyanide), an alkyl halide, and an acid chloride or nitrile, respectively. The modular assembly employs sequential deprotonation-alkylation and deprotonation-acylation or imination of Asmic, followed by an unusual carbon-sulfur bond cleavage to construct the azole. The strategy is robust, highly efficient, and affords C4-C5 disubstituted oxazoles or imidazoles in a single operation

Automated summary

Substituted oxazoles and imidazoles can be synthesized in one pot using the isocyanide building block Asmic, an alkyl halide, and an acid chloride or nitrile. The modular assembly involves sequential deprotonation-alkylation and deprotonation-acylation or imination of Asmic, followed by a unique carbon-sulfur bond cleavage to construct the azole. This strategy is robust, highly efficient, and allows for the formation of C4-C5 disubstituted oxazoles or imidazoles in a single operation.