Iodine-Promoted Oxidative Cyclization of Acylated and Alkylated Derivatives from Epoxides toward the Synthesis of Aza Heterocycles

Alageswaran Jayaram; Karthick Govindan; Vijaya Raghavan Kannan; Vijay Thavasianandam Seenivasan; Nian-Qi Chen; Wei-Yu Lin

doi:10.1021/acs.joc.2c02802

Iodine-Promoted Oxidative Cyclization of Acylated and Alkylated Derivatives from Epoxides toward the Synthesis of Aza Heterocycles

J Org Chem. 2023 Feb 3;88(3):1749-1761. doi: 10.1021/acs.joc.2c02802. Epub 2023 Jan 17.

Authors

Alageswaran Jayaram¹, Karthick Govindan¹, Vijaya Raghavan Kannan¹, Vijay Thavasianandam Seenivasan¹, Nian-Qi Chen¹, Wei-Yu Lin^{1

2

3}

Affiliations

¹ Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, ROC.
² Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan, ROC.
³ Drug Development and Value Creation Research Centre, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, ROC.

PMID: 36649653
DOI: 10.1021/acs.joc.2c02802

Abstract

A new method for directly synthesizing acylated and alkylated quinazoline derivatives by the epoxide ring-opening reaction in the presence of I₂/DMSO with 2-aminobenzamide is described herein. The developed mild protocol is efficient and displays a wide variety of functional group tolerance and substrate-controlled high selectivity, and the application of a continuous flow technique allows for faster reaction time and higher yields. Moreover, the robustness of the method is applicable in gram-scale synthesis.