1,3-Dipolar cycloaddition of nitrones: synthesis of multisubstituted, diverse range of heterocyclic compounds

Abstract

The 1,3-dipolar cycloaddition reaction of nitrone is one of the most important methods for the synthesis of different sizes of heterocycles which have enormous applications in natural products, biologically active molecules and pharmaceuticals.

Unveiling the intramolecular [3 + 2] cycloaddition reactions ofC,N-disubstituted nitrones from the molecular electron density theory perspective

“…Some noteworthy conclusions can be derived from the energy profile study. (1) The IM32CA reactions of 20, 24 and 26 show negative reaction free energies from À15.8 to À17.9 kcal mol À1 and are therefore kinetically controlled. (2) The activation energies of TS5 and TS6 differ minimally by 0.4 kcal mol À1 in toluene.…”

“…Some noteworthy conclusions can be derived from the energy profile study. (1) The IM32CA reactions of 15 and 18 show negative reaction free energies and are therefore kinetically controlled. (2) The 32CA reaction of nitrone 15 is completely regioselective along the r 1 reaction path as the activation energy of TS1 is lowered than that of TS2 by 3.9 kcal mol À1 in toluene.…”

“…The [3 + 2] cycloaddition (32CA) reactions of nitrones to alkenes serve as one of the classic methodologies for the preparation of isoxazolidines 1 and have received widespread attention owing to the high stability and pharmacological utility of the synthesized adducts. 2,3 These reactions require heating nitrone 1 with alkene 2 in an inert solvent, leading to the targeted isoxazolidine 3 (Scheme 1) in reasonably good yields.…”

Efficient Catalytic Synthesis of Condensed Isoxazole Derivatives via Intramolecular Oxidative Cycloaddition of Aldoximes

“…Thus, 10 mol% of 2-iodobenzoic acid 2a is the most suitable for the reaction. Other iodine reagents 2 were found less efficient (entries 1, [15][16][17][18].…”

“…The 1,3-dipole cycloaddition reaction is one of the most powerful methods to construct five-membered heterocycles [16][17][18][19][20][21][22][23][24][25][26]. The cycloaddition of nitrile oxides with alkenes and acetylenes is often used in the synthesis of isoxazoles and isoxazolines [27][28][29][30][31][32][33][34][35][36][37].…”