Synthesis of 3-Substituted 5,5-Dimethyl Isoxazolines via Unusual Reactivity of Chlorooximes and Di-tert-butyl Dicarbonate (Boc2O) or tert-Butyl Acetate (t-BuOAc)

Abstract

A convenient method for the synthesis of 3-substituted 5,5-dimethyl isoxazolines from diversely functionalized chlorooximes and di-tert-butyl dicarbonate (Boc₂O) has been demonstrated. The reaction proceeds via [3 + 2] cycloaddition of isobutene, generated in situ from Boc₂O and nitrile oxides, formed from chlorooximes. tert-Butyl acetate (tert-BuOAc) also proved to be an efficient alternative source of isobutene, providing a comparable yield of desired isoxazolines under similar conditions. It has also been demonstrated that the in situ preparation of chlorooximes from corresponding aldoximes using N-chlorosuccinimide (NCS) and their direct utilization for one-pot synthesis of 3-substituted 5,5-dimethyl isoxazolines can be successfully achieved. This process occurs without the need for metal catalysts or bases. The method features several advantages, including the use of readily accessible reagents, broad substrate scope, high yields, and reliability on a gram scale, making it a valuable approach for the synthesis of 3-substituted 5,5-dimethyl isoxazolines.