Copper-Catalyzed [3 + 2] Cycloaddition Reaction of N-Hydroxysuccinimide Ester with Isocyanoacetates for the Synthesis of 4,5-Disubstituted Oxazoles

Abstract

The cycloaddition reaction of N-hydroxysuccinimide ester and isocyanatoacetate catalyzed by copper was described. A series of 4,5-disubstituted oxazole compounds, including ones derived from natural fatty acids, drugs, amino acids, and peptides, were obtained in moderate to high yields. The derivatization reaction was explored. The reaction mechanism was discussed.

Synthesis of N-Hydroxysuccinimide Esters, N-Acylsaccharins, and Activated Esters from Carboxylic Acids Using I2/PPh3

“…This compound was eluted using 20:80 EtOAc/hexane solvent (white solid, 273 mg, 92%). mp 153–154 °C; R f = 0.60 (20:80 EtOAc/hexanes); the spectroscopic data is identical to that reported in the literature …”

“…mp 153−154 °C; R f = 0.60 (20:80 EtOAc/hexanes); the spectroscopic data is identical to that reported in the literature. 35 1 H NMR (400 MHz, CDCl 3 ): δ 8.25 (1H, app t, J = 2.0 Hz), 8.07−8.03 (1H, m), 7.80 (1H, ddd, J = 8.0, 2.0, 1.1 Hz), 7.39 (1H, app t, J = 8.0 Hz), 2.89 (4H, s); 13 2,5-Dioxopyrrolidin-1-yl 4-Nitrobenzoate (3d). Prepared using general procedure 1.…”

“…mp 148−150 °C; R f = 0.48 (50% EtOAc/ Hexane); the spectroscopic data is identical to that reported in the literature. 35 1H NMR (500 MHz, CDCl 3 ): δ 5.02 (s, 1H), 4.70 (1H, t, J = 7.8 Hz), 2.84 (4H, s), 1.57 (3H, d, J = 7.3 Hz), 1.45 (9H, s); 13 C{ 1 H} NMR (125 MHz, CDCl 3 ): δ 169.2, 168.7, 154.8, 80.7, 47.8, 28.4, 25.7, 18.9; HRMS (DART) m/z: calcd for C 12 H 22 N 3 O 6 [M + NH 4 ] + , 304.1497; found, 304.1503.…”

Recent Advancements in Strategies for the Synthesis of Imidazoles, Thiazoles, Oxazoles, and Benzimidazoles

“…4.5‐disubstituted oxazole scaffolds are crucial building blocks in many drugs and natural products. An efficient copper‐catalyzed synthetic procedure has been devised by Wu et al [96] . in 2023 involving functionalized N ‐hydroxysuccinimide ester 131 and isocyanatoacetate 55 in the presence of DMF as solvent at ambient temperature via the [3+2] cycloaddition reaction (Scheme 74).…”

“…4.5-disubstituted oxazole scaffolds are crucial building blocks in many drugs and natural products. An efficient coppercatalyzed synthetic procedure has been devised by Wu et al [96] in 2023 involving functionalized N-hydroxysuccinimide ester 131 and isocyanatoacetate 55 in the presence of DMF as solvent at ambient temperature via the [3 + 2] cycloaddition reaction (Scheme 74). Functional group tolerance of the optimized reaction conditions was performed involving various EDG, EWG substituted 131, as well as 131 containing heteroaromatic substituents.…”