Stereoconvergent and stepwise 1,3-dipolar cycloadditions of nitrile oxides and nitrile imines

The first example of stereoconvergent 1,3-dipolar cycloaddition of nitrile oxides and nitrile imines with E/Z isomeric mixture of electron-deficient olefins is reported, delivering isoxazolines and pyrazolines bearing two vicinal stereogenic tertiary and trifluoromethylated quaternary carbon centers with perfect regio-and diastereoselectivities. The possibility of concerted cycloaddition/epimerization sequence under basic condition to form the thermodynamically stable diastereomers is excluded through some control experiments and DFT calculations, and a stepwise mechanism is proposed. (C) 2021 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

This paper reports the first example of a stereoconvergent reaction involving 1,3-dipolar cycloaddition of nitrile oxides and nitrile imines with electron-deficient olefins. The reaction produces compounds with multiple stereogenic centers and exhibits excellent regio- and diastereoselectivities. Through control experiments and calculations, the possibility of thermodynamically stable diastereomers formation during the reaction is ruled out, and a stepwise mechanism is proposed.