Substituent-Controlled Selective Synthesis of N‑Acyl 2‑Aminothiazoles by Intramolecular Zwitterion-Mediated C–N Bond Cleavage

• Published in: Journal of organic chemistry Vol. 79; no. 22; pp. 11146 - 11154
• Main Authors: Wang, Yang, Zhao, Fei, Chi, Yue, Zhang, Wen-Xiong, Xi, Zhenfeng
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 21.11.2014; Amer Chemical Soc
• Subjects: chemical bonding; chemical reactions; chemical structure; Chemistry; Chemistry, Organic; chlorides; cleavage (chemistry); hydrogen; lithium; organic chemistry; organic compounds; Physical Sciences; Science & Technology; HOFMANN ELIMINATION; COORDINATION CHEMISTRY; CROSS-COUPLING REACTION; CARBON-NITROGEN; BIOLOGICAL EVALUATION; H BONDS; CANCER-CELL MIGRATION; EARTH-METAL COMPLEXES; THIAZOLE DERIVATIVES; CATALYTIC ADDITION
• ISSN: 0022-3263; 1520-6904; 1520-6904
• DOI: 10.1021/jo502123k

The cleavage of C–N bonds is an interesting and challenging subject in modern organic synthesis. We have achieved the first zwitterion-controlled C–N bond cleavage in the MCR reaction among lithium alkynethiolates, bulky carbodiimides, and acid chlorides to construct N-acyl 2-aminothiazoles. This is a simple, highly efficient, and general method for the preparation of N-acyl 2-aminothiazoles with a broad range of substituents. The selective synthesis of N-acyl 2-aminothiazoles significantly depends on the steric hindrance of carbodiimides. The result is in striking contrast with our previous convergent reaction giving 5-acyl-2-iminothiazolines via 1,5-acyl migration. It is indeed interesting that the slight change of the substituents on the carbodiimides can completely switch the product structure. Experimental and theoretical results demonstrate the reason why the C–N bond cleavage in the present system is prior to the acyl migration. The intramolecular hydrogen relay via unprecedented Hofmann-type elimination is essential for this totally new zwitterion-controlled C–N bond cleavage.