A Simple and Efficient One‐Pot Synthesis of 3‐Acylisoxazolines from Alcohols and α‐Nitro Ketones in the Presence of NaHSO₄/SiO₂

Abstract

A simple and efficient method for the synthesis of 3‐acylisoxazolines has been developed using alcohols and α‐nitro ketones in the presence of NaHSO4/SiO2. The alcohols and α‐nitro ketones are initially converted into alkenes and nitrile oxides, respectively, and then react with one another to give 3‐acylisoxazolines. This procedure, using alcohols, gave the desired dihydroisoxazoles more effectively than the conventional procedure using alkenes as starting materials. The reaction proceeded through three pathways depending on the type of alcohol used; reactions between nitrile oxides and (I) endo and exo alkenes, (II) dimerized alkenes and (III) single alkenes. Most of the reactions proceeded efficiently and gave the corresponding 3‐acylisoxazolines in good to excellent yield.

Synthetic Diversity from a Versatile and Radical Nitrating Reagent

“…Nitrile oxide dipoles are known to operate under electronic control with similar magnitudes in HOMO–LUMO interactions and are highly susceptible to weak perturbations . However, upon closer examination the observed selectivity in all cases is (1) consistent with similarly reported nitrile oxide cycloaddition reactions and (2) a classic frontier molecular orbital interpretation of the two reactants . In each case, the regioselectivity of the cycloadditions displayed in Table is consistent with a LUMO‐controlled dipole (nitrile oxide), which is further increased by the lowering of the LUMO energy by the pendent acyl group (Scheme ).…”

Pd-Catalysed [3 + 2]-cycloaddition towards the generation of bioactive bis-heterocycles/identification of COX-2 inhibitors via in silico analysis

“…They are also very good substrates for [3 + 2] dipolar cycloadditions under mild reaction conditions to access a variety of five-membered heterocyclic ring systems such as isoxazoles, isoxazolines, and oxadiazoles. 9 Various reagents such as α-nitro ketones, 10 ethyl nitro-acetate, 11,12 ethanamine, 13 and diazoesters 14 were reported in the literature as precursors for the in situ generation of nitrile oxides. Usually, a 1,3-dipolar cycloaddition of nitrile oxides with alkenes or alkynes is involved to generate five-membered heterocyclic ring systems.…”

Stereoselective Synthesis of 4,5‐Dihydroisoxazole Derivatives from 1,1‐Dicyanocyclopropanes and Hydroxylamine Hydrochloride

“…Additionally, polysubstituted isoxazolines as versatile intermediates exhibit superior applications in organic synthesis [28–40] . Accordingly, not surprisingly, numerous synthetic approaches leading to an isoxazoline nucleus have been developed, principally consisting of the cycloaddition from 1,3‐dicarbonyl intermediates and hydroxylamine or from modified three‐carbon 1,3‐electrophilic intermediates of 1,3‐dicarbonyl compounds, including β‐alkylthioenones, enamino ketones, ynones, and α,β‐unsaturated ketones [41–46] . Another most efficient strategy based on the 1,3‐dipolar cyclic addition reactions of alkenes or alkynes and nitrile oxides, formed readily from aldoximes or nitroalkanes, also was burgeoned [47–61] .…”