Development of regioselective [2 + 3] cycloaddition reactions of nitrile oxides with alkenes using intramolecular reactions through oxime groups [1]

Abstract

Nitrile oxides afford 2-isoxazoline heterocycles through [2 + 3] cycloaddition reactions with alkenes. These heterocycles can be converted to useful intermediates, such as β-hydroxy ketones and γ-amino alcohols, leading to pharmaceutical and agrochemical compounds. However, nitrile oxides directly connected to a carbonyl group show low reactivity owing to the decrease in energy of the dipole HOMO. Furthermore, when dissymmetric internal alkenes are used, regioselective control is difficult. Herein, we have designed nitrile oxides bound to alkenes through the oxime group and demonstrated their intramolecular [2 + 3] cycloaddition reactions. The desired cycloadducts were obtained in high yields and as single regioisomers. Furthermore, face-selective cycloaddition reactions were achieved by introducing a stereocenter into the linker moiety, affording the desired cycloadducts with good diastereoselectivity.