Synthesis of 7-Arylthiomethyl Dibenzo[ b, d]azepines through Imidoylative Heck Cyclization and CPA-Catalyzed Thio-Michael Addition/Enantioselective Protonation

Weiming Hu; Xilong Wang; Yan Peng; Shuang Luo; Jiaji Zhao; Qiang Zhu

doi:10.1021/acs.orglett.2c01217

Synthesis of 7-Arylthiomethyl Dibenzo[ b, d]azepines through Imidoylative Heck Cyclization and CPA-Catalyzed Thio-Michael Addition/Enantioselective Protonation

Org Lett. 2022 May 27;24(20):3642-3646. doi: 10.1021/acs.orglett.2c01217. Epub 2022 May 13.

Authors

Weiming Hu^{1

2}, Xilong Wang^{1

2}, Yan Peng^{1

2}, Shuang Luo^{1

2}, Jiaji Zhao³, Qiang Zhu^{1

2

4}

Affiliations

¹ State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Guangzhou 510530, China.
² University of Chinese Academy of Sciences, No. 19(A) Yuquan Road, Shijingshan District, Beijing 100049, China.
³ School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan 528400, China.
⁴ Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, College of Chemistry and Materials, Nanning Normal University, Nanning 530001, China.

PMID: 35549333
DOI: 10.1021/acs.orglett.2c01217

Abstract

A chiral phosphoric acid-catalyzed thio-Michael addition/enantioselective protonation has been developed for the first time. The reaction applies 7-methylene-6-aryl-7H-dibenzo[b,d]azepines, products of Pd-catalyzed imidoylative Heck cyclization, as Michael acceptors in reactions with a wide range of aryl thiols. Diversified 7-[(arylthio)methyl]-7H-dibenzo[b,d]azepines bearing a benzylic stereocenter and a thermodynamically regulated biaryl axis were produced with good to excellent enantioselectivity and 14-25:1 diastereoisomeric ratios.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Azepines*
Catalysis
Cyclization
Stereoisomerism

Substances

Azepines