Synthesis of 3-Acyl-isoxazoles and Δ2-Isoxazolines from Methyl Ketones, Alkynes or Alkenes, and tert-Butyl Nitrite via a Csp3-H Radical Functionalization/Cycloaddition Cascade

Peng Dai; Xin Tan; Qian Luo; Xiang Yu; Shuguang Zhang; Fang Liu; Wei-Hua Zhang

doi:10.1021/acs.orglett.9b01683

Synthesis of 3-Acyl-isoxazoles and Δ²-Isoxazolines from Methyl Ketones, Alkynes or Alkenes, and tert-Butyl Nitrite via a Csp³-H Radical Functionalization/Cycloaddition Cascade

Org Lett. 2019 Jul 5;21(13):5096-5100. doi: 10.1021/acs.orglett.9b01683. Epub 2019 Jun 13.

Authors

Peng Dai¹, Xin Tan¹, Qian Luo¹, Xiang Yu¹, Shuguang Zhang¹, Fang Liu¹, Wei-Hua Zhang¹

Affiliation

¹ Jiangsu Key Laboratory of Pesticide Science , College of Sciences, Nanjing Agricultural University , Nanjing 210095 , China.

PMID: 31194561
DOI: 10.1021/acs.orglett.9b01683

Abstract

A novel metal-free tandem Csp³-H bond functionalization of ketones and 1,3-dipolar cycloaddition has been developed. An efficient approach to a variety of oxazole and isoxazoline derivatives is demonstrated using the 1,3-dipolar cycloaddition of alkynes and alkenes to nitrile oxides generated by reactions of methyl ketones with tert-butyl nitrite. This new protocol provides access to a variety of isoxazolines with diverse functionalities. An isoxazole generated in this way was found to have significant antifungal activity.