Synthesis 2017; 49(21): 4876-4886
DOI: 10.1055/s-0036-1590810
paper
© Georg Thieme Verlag Stuttgart · New York

Efficient One-Pot Synthesis of 2,4-Disubstituted Thiazoles and Dimeric Thiazoles Directly from Acyl Chlorides and β-Azido Disulfides

Yi Liu*a, Zhi Lia, Yichuan Xiea, Peng Heb, Junfei Qiaob, Xinyuan Fanc, Yuguo Du*b
  • aSchool of Chemistry and Chemical Engineering, Yantai University, 30 Qingquan Rd, Laishan District, Yantai, 264005, P. R. of China   Email: liuyi@ytu.edu.cn
  • bState Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, P. R. of China   Email: yuguodu@rcees.ac.cn
  • cInstitute of Advanced Synthesis, Nanjing Tech University, Nanjing, 210009, P. R. of China
This work was supported by the NNSFC projects (21402192, 21372254 and 21672255).
Further Information

Publication History

Received: 26 April 2017

Accepted after revision: 31 May 2017

Publication Date:
26 July 2017 (eFirst)

Abstract

A simple and effective one-pot cascade procedure to provide 2,4-disubstituted thiazoles and symmetrical dimeric thiazoles directly from commercially available acid chlorides and β-azido disulfides in moderate to high yields is described. This cascade transformation consists of disulfide cleavage, thiocarbonylation, phosphine-promoted intramolecular Staudinger/aza-Wittig reaction and dehydrogenation to form the corresponding thiazoles. The application of our methodology is demonstrated by the concise two-step synthesis of anticancer agent SMART and its O-linked dimer in 64% and 46% overall yields, respectively. This directed cascade reaction could be easily handled and scaled up under mild conditions, enabling the construction of focused thiazole derivatives for further pharmacological evaluation.

Supporting Information