Divergent Synthesis of Cyclopropanated Tetrahydroquinolines by Tandem Functionalization of Quinoline Derivatives

Jianjie Chen; Jian Yang; Min Zhang

doi:10.1021/acs.joc.4c00783

Divergent Synthesis of Cyclopropanated Tetrahydroquinolines by Tandem Functionalization of Quinoline Derivatives

J Org Chem. 2024 May 16. doi: 10.1021/acs.joc.4c00783. Online ahead of print.

Authors

Jianjie Chen¹, Jian Yang¹, Min Zhang¹

Affiliation

¹ Key Lab of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Wushan Road-381, Guangzhou 510641, P. R. China.

PMID: 38754033
DOI: 10.1021/acs.joc.4c00783

Abstract

Here, reported is a new method for divergent synthesis of functionalized tetrahydroquinolines (THQs), featuring a biomedically interesting azabicyclo[4.1.0]heptane core, proceeding with mild conditions, good substrate and functionality tolerance, and operational simplicity. Mechanistic studies suggest that the products are formed via carbonucleophilic 1,4-addition-induced dearomatization of quinolinium salts and intramolecular cyclopropanation with α-halo ketones followed by α-nucleophilic addition with different nucleophiles. The present work lays a foundation to access new N-heterocycles via the dearomative tandem functionalization of azaarenes.