Synthesis of 2-Substituted Thiazolines via Efficient Tandem C–X/C–S Bond Formation

Abstract

Five-membered N,S-heterocyclic 2-thiazolines are important scaffolds in natural products, pharmaceuticals, food flavors, and chiral ligands. Due to their extensive applications, the synthesis of these valuable molecules has been widely investigated in recent years. Despite advances, efficient methods that avoid expensive/toxic reagents and harsh conditions, while delivering high yields, are still needed. In this study, we developed an efficient synthetic route to two kinds of 2-substituted thiazolines via a tandem reaction that constructs both exocyclic C–X (X = S or P) and endocyclic C–S bonds. A relatively diverse range of 2-(organothio)thiazolines and 2-phosphorylthiazolines were obtained in moderate to high yields under mild conditions from commercially available S/P-nucleophiles and 2-chloroethyl isothiocyanate in the presence of a common base. This tandem C–X/C–S bond formation methodology features generally high output, rapid conversion, and good substrate scope under mild and operationally simple conditions.