Applications of 3,5‐Dialkyl‐4‐nitroisoxazoles and Their Derivatives in Organic Synthesis^#

Abstract

Dedicated to Prof. A. Ramachandraiah on his superannuation from the servicesThe methyl/methylene group present at the 5 th position of 3,5dialkyl-4-nitroisoxazoles show characteristic reactivity because of the presence of À NO 2 at the 4 th position in the structure. This methyl/methylene is used for the generation of carbanion that undergo Knoevenagel condensation, vinylogous nitroaldol (Henry type), Mannich and Michael addition reactions. The unsaturated systems generated by Knoevenagel condensation are used for 1,4-and 1,6-Michael addition, epoxidation, aziridination, cycloaddition (cascade/domino/tandem and dihydroxylation reactions. This resulted into the generation of many functionalized and complex organic molecules in asymmetric and racemic forms. Along with these, the isoxazole moiety has also been used as À COOH equivalent by basic/oxidative hydrolysis. This review describes recent literature on the synthetic applications of 3,5dialkyl-4-nitroisoxazoles and their derivatives for the generation of functionalized/complex heterocyclic compounds using above mentioned type of reactions and concepts.

Direct 1,6-Difluoromethylation of 3-Methyl-4-nitro-5-styryl Isoxazoles by Photoredox-Promoted Radical Addition

“…Adamo and co-workers developed 3-methyl-4-nitro-5-alkenyl-isoxazole 1 , bearing a γ,δ-unsaturated alkene skeleton, which is an excellent 1,6-Michael acceptor and shows high reactivity toward soft stabilized nucleophiles. Compared to the many reports on nucleophilic 1,6-addition of 1 , the selective radical 1,6-addition is difficult and rarely reported, with the exception of p -methylene benzoquinones . This is due to the competing side reactions, such as 1,4-radical additions and free radical polymerization.…”

Asymmetric Organocatalysis—A Powerful Technology Platform for Academia and Industry: Pregabalin as a Case Study

“…They employed the Cinchona-derived phase-transfer catalyst 20 for the conjugate addition of nitromethane to 17. The key material 17 was based on their brand α,β-unsaturated acid acceptor surrogates derived from 3,5-dimethyl-4-nitroisoxazole 16 [54]. Phase-transfer catalysis imparted good enantioselectivity in the Michael addition (72% ee); further recrystallisation was able to yield enantiopure 18 (>99% ee), with an impact on the yield.…”

Vinylogous Nitro-Haloform Reaction Enables Aromatic Amination

“… 14 Most significantly, our previous studies demonstrated the existence of profound analogies between the reactivity of heteroaromatic vinylogous nitromethanes, such as 6 , and carbonyl species such as methylketones 1 ( Figure 1 ). 15 …”