Solvent and Catalyst-Free Mechanochemical C(sp3)-S Cross-Coupling/Cyclization/Dehydration Cascade:
Vipin Kumar1, Anup Kumar Yadav1, Malkeet Singh1
1Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
Abstract:
Mechanochemistry has emerged as a powerful tool for enabling solvent-free, energy-efficient, and sustainable chemical transformation. Herein, we report a mechanochemical strategy for the direct synthesis of 2,3-dihydrothiazoles and thiazolidines employing easily accessible β-ketothioamides and α-bromoketones/1,3-dichloroprop-2-one under solvent-free condition in a mortar and pestle at room temperature within 15 min. The reaction proceeds via consecutive C(sp3)-S cross-coupling/intramolecular cyclization/dehydration cascade affording higher yields compared to solution-based traditional methods, which typically require reaction times of several hours. This process features operationally simple mild condition, short reaction time, chemo-/regioselectivity, broad substrate scope, good functional group compatibility, excellent yields, facile scalability, and overcomes key synthetic challenges. Noteworthy, stereochemistry of the exocyclic double bond was assigned to have Z-configuration.
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