Temperature-Controlled Thiation of α-Cyano-β-Alkynyl Carbonyl Derivatives for De Novo Synthesis of 2-Aminothiophenes and Thieno[2,3- c]isothiazoles

Tzu-Ting Kao; Po-Kai Peng; Min-Chieh Liang; Chia-Jui Lee; I-Chia Chen; Kak-Shan Shia; Yen-Ku Wu

doi:10.1021/acs.joc.8b01866

Temperature-Controlled Thiation of α-Cyano-β-Alkynyl Carbonyl Derivatives for De Novo Synthesis of 2-Aminothiophenes and Thieno[2,3- c]isothiazoles

J Org Chem. 2018 Dec 7;83(23):14688-14697. doi: 10.1021/acs.joc.8b01866. Epub 2018 Oct 12.

Authors

Tzu-Ting Kao¹, Po-Kai Peng², Min-Chieh Liang², Chia-Jui Lee¹, I-Chia Chen³, Kak-Shan Shia¹, Yen-Ku Wu²

Affiliations

¹ Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes , Miaoli 35053 , Taiwan.
² Department of Applied Chemistry , National Chiao Tung University , 1001 University Road , Hsinchu 30010 , Taiwan.
³ Department of Cosmetic Applications and Management , Cardinal Tien Junior College of Healthcare and Management , New Taipei City 23143 , Taiwan.

PMID: 30277073
DOI: 10.1021/acs.joc.8b01866

Abstract

Making use of temperature-controlled thiation as a key operation, a simple route to 2-aminothiophenes or thieno[2,3- c]isothiazoles has been newly developed wherein the 2-aminothiophene nucleus was formed through an initial formation of thioamide followed by a 5-exo-dig addition to the tethered alkyne; however, under harsher thermal conditions, excess sulfur-transferring reagents enabled further oxidative thiation to generate the corresponding thieno[2,3- c]isothiazoles.

Publication types

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