Metal-Free C-2-H Alkylation of Quinazolin-4-ones with Alkanes via Cross-Dehydrogenative Coupling

Shuai Mao†§⊥, Kaixiu Luo‡⊥, Lu Wang†, Hong-Yi Zhao†, Andrea Shergalis§, Minhang Xin†, Nouri Neamati*§, Yi Jin*‡, and San-Qi Zhang*†

†Department of Medicinal Chemistry, School of Pharmacy, Xi’an Jiaotong University , Xi’an 710061 ,China

‡Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University , Kunming 650091 ,P. R. China

§Department of Medicinal Chemistry, College of Pharmacy,University of Michigan, Ann Arbor , Michigan 48109 ,United States

Organic Letters, Article ASAP

DOI:10.1021/acs.orglett.9b00638

Publication Date (Web): March 25, 2019

Abstract

A practically useful approach for the cross-dehydrogenative coupling of quinazolin-4-one with simple nonactivated alkanes is reported. The products were smoothly formed under mild reaction conditions, within short reaction time at ambient temperature. The formation of new Csp3-Csp2bonds occurred at the electron-poor C-2 position ofquinazolin-4-one. The approach has the potential to be an important tool for the late-stage functionalization of advanced synthetic intermediates and may find many applications in medicinal chemistry.

全文链接：https://pubs.acs.org.ccindex.cn/doi/abs/10.1021/acs.orglett.9b00638