Base-Controlled Divergent Synthesis of Fluorine-Containing Benzo[4,5]imidazo[2,1- b][1,3]thiazines from 2-Mercaptobenzimidazoles and β-CF3-1,3-Enynes

Zhi-Qing He; Shu-Jie Chen; Guo-Shu Chen; Jin-Hao Lin; Jia-Ming Wu; Yun-Lin Liu

doi:10.1021/acs.joc.3c01570

Base-Controlled Divergent Synthesis of Fluorine-Containing Benzo[4,5]imidazo[2,1- b][1,3]thiazines from 2-Mercaptobenzimidazoles and β-CF₃-1,3-Enynes

J Org Chem. 2023 Sep 15;88(18):13262-13271. doi: 10.1021/acs.joc.3c01570. Epub 2023 Aug 24.

Authors

Zhi-Qing He¹, Shu-Jie Chen¹, Guo-Shu Chen¹, Jin-Hao Lin¹, Jia-Ming Wu¹, Yun-Lin Liu^{1

2

3}

Affiliations

¹ School of Chemistry and Chemical Engineering, Guangzhou University, Guangzhou 510006, P. R. China.
² Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu 610106, China.
³ Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.

PMID: 37619215
DOI: 10.1021/acs.joc.3c01570

Abstract

A base-controlled divergent cyclization between 2-mercaptobenzimidazoles and β-CF₃-1,3-enynes providing either trifluoromethylated or fluorinated benzo[4,5]imidazo[2,1-b][1,3]thiazines has been developed. The β-CF₃-1,3-enyne, as a three-carbon synthon, underwent a 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU)-catalyzed tandem hydroamination/intramolecular hydrothiolation to give CF₃-substituted 3,4-dihydro-2H-benzo[4,5]imidazo[2,1-b][1,3]thiazine, whereas reaction with KOH afforded fluorinated 4H-benzo[4,5]imidazo[2,1-b][1,3]thiazine exclusively. In addition, the synthetic utility of this methodology was showcased through a variety of downstream derivatizations.