Multicomponent Reactions with Cyclic Tertiary Amines Enabled by Facile C-N Bond Cleavage

Qiming Zhu; Qinghe Yuan; Mingwei Chen; Mengping Guo; Hanmin Huang

doi:10.1002/anie.201612017

Multicomponent Reactions with Cyclic Tertiary Amines Enabled by Facile C-N Bond Cleavage

Angew Chem Int Ed Engl. 2017 Apr 24;56(18):5101-5105. doi: 10.1002/anie.201612017. Epub 2017 Apr 3.

Authors

Qiming Zhu¹, Qinghe Yuan¹, Mingwei Chen¹, Mengping Guo¹, Hanmin Huang²

Affiliations

¹ Key Laboratory of Natural Active Pharmaceutical Constituents of Jiang Xi Province, College of Chemistry and Bio-engineering, Yichun University, Yichun, 336000, P.R. China.
² Department of Chemistry, University of Science and Technology of China, Hefei, 230026, P.R. China.

PMID: 28370927
DOI: 10.1002/anie.201612017

Abstract

A novel and catalyst-free multicomponent reaction with cyclic tertiary amines, electron-deficient aryl halides or heteroaromatic halides, and Na₂ S enabled by facile C-N bond cleavage of the cyclic tertiary amines was developed. This direct and operationally simple method can be applied with a wide range of functional groups and provides an efficient and rapid approach to potentially drug-like products containing amine, azaarene, thioether, or phenol ether functionalities in good to excellent yields. The utility of this method was demonstrated by the rapid synthesis of the analgesic ruzadolane.

Keywords: C−N bonds; C−S bonds; catalyst-free reactions; multicomponent reaction; tertiary amines.

Publication types

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