Efficient regioselective synthesis of 4‐ and 5‐substituted isoxazoles under thermal and microwave conditions

Abstract

The [2+3] cycloaddition reaction between nitrile oxides 2 and the captodative olefins 1 or the methyl crotonate derivatives 4 is regioselective and leads to the formation of the 5-substituted amino-isoxazole 3 or the 4-substituted methoxycarbonyl-isoxazole 5 derivatives, respectively. All these reactions are greatly accelerated by microwave irradiation without changing their regioselectivity with respect to the thermal conditions.

General Platform for the Conversion of Isoxazol‐5‐ones to 3,5‐Disubstituted Isoxazoles via Nucleophilic Substitutions and Palladium Catalyzed Cross‐Coupling Strategies

“…Purification by flash column chromatography (SiO 2 , gradient: Hex – 95:5 Hex/AcOEt – 9:1 Hex/AcOEt) affords the title compound as a brown solid: 50 mg, quantitative. 1 H (500 MHz, CDCl 3 ) δ:7.72–7.71 (m, 2H), 7.41–7.37 (m, 5H), 7.34–7.32 (m, 2H), 7.20–7.17 (m, 1H), 5.47 (s, 1H), 3.48 (s, 3H). 13 C (125 MHz, CDCl 3 ) δ: 169.8, 163.8, 145.0, 130.1, 129.9, 129.6, 128.9, 126.8, 125.4, 123.0, 78.8, 38.5.…”

Ketene Three‐Component Reaction: A Metal‐Free Multicomponent Approach to Stereodefined Captodative Olefins

“…The stereoselective synthesis of polysubstituted alkenes remains one of the most interesting subjects in organic synthesis. Captodative olefins, alkenes with both an electron‐withdrawing and an electron‐donating group at the α‐carbon,1 have proved to be very versatile synthons for cycloadditions,2 Friedel–Crafts reactions,3 and natural product synthesis 4. Furthermore, the presence of substituents at the β‐position strongly modifies both stereo and regioselectivity,5 thus rendering these compounds particularly appealing.…”

The synthetic and therapeutic expedition of isoxazole and its analogs

“…The [2+3] cycloaddition reaction of nitrile oxides with captodative olefins or methyl crotonate derivatives is regioselective (Route e, Fig. 4) and leads to the formation of the 5substituted amino-isoxazole or the 4-substituted methoxycarbonyl-isoxazole derivatives, respectively (Lasri et al 2008). The [4+1] cycloaddition reaction of isocyanides with α-haloketone oxime (Route f, Fig.…”