General Synthesis of N-CF3 Heteroaryl Amides via Successive Fluorination and Acylation of Sterically Hindered Isothiocyanates

Min Tao; Jiasheng Qian; Zuanguang Chen; Lin-Kun An; David M Wilson; Jianbo Liu

doi:10.1021/acs.joc.3c01740

General Synthesis of N-CF₃ Heteroaryl Amides via Successive Fluorination and Acylation of Sterically Hindered Isothiocyanates

J Org Chem. 2023 Nov 3;88(21):15237-15248. doi: 10.1021/acs.joc.3c01740. Epub 2023 Oct 12.

Authors

Min Tao¹, Jiasheng Qian¹, Zuanguang Chen¹, Lin-Kun An¹, David M Wilson², Jianbo Liu³

Affiliations

¹ School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Guangdong, China.
² Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California 94158, United States.
³ Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, China.

PMID: 37823733
DOI: 10.1021/acs.joc.3c01740

Abstract

We report the one-pot synthesis of N-CF₃ heteroaryl amides (NTFMHA) from heteroaryl carboxylic acids and sterically hindered isothiocyanates, including various amino acid analogues, in the presence of AgF. The key to this reaction is the utilization of free heteroaryl acyl chlorides, rather than their corresponding hydrochloride salts. This method represents a complementary method of our previous work and enables modification to a variety of previously inaccessible structures, including α-tertiary amines and N-CF₃-modified pharmaceuticals.