Ring Closure of Nitroalkylmalonates for the Synthesis of Isoxazolines under the Acylation Conditions

Abstract

Acylation of nitroalkylmalonates was found to yield substituted isoxazoline derivatives. This redox‐neutral transformation has a wide substrate scope and produces target products with yields up to 92%. Various substituents (aryl, alkyl, and ester) at the C3 and C4 positions of the resulting isoxazolines were also tolerated. A quick assembly of the isoxazoline ring starting from nitroalkenes and malonates was successfully developed. Control experiments showed that the intramolecular ring closure is the most likely key mechanistic step. Subsequent transformations into pyrrolidine and furane derivatives demonstrated the synthetic utility of the obtained products.

Nitrile Oxide, Alkenes, Dipolar Cycloaddition, Isomerization and Metathesis Involved in the Syntheses of 2-Isoxazolines

“…In August 2022, a new and promising synthetic procedure led to isoxazolines under mild conditions. The approach uses simple reagents with broad tolerance scope for versatile reagents— Scheme 276 [ 307 ]. In this work, 3,4,5,5–tetrasubstituted isoxazolines were obtained from nitroalkylmalonates via redox-neutral ring-closure reaction as a crucial step.…”

“… Syntheses of 3,4,5,5-tetrasubstituted isoxazolines equipped with two EWG group (CO 2 Me in most cases) substituents in position 5,5 [ 307 ]. EWG 1 , EWG 2 , R 1 , R 2 = COOMe, COOMe, Me, 3,4,5-(MeO) 3 C 6 H 2 ; COOMe, COOMe, Me, 5-bromofuran-2-yl; COOBn, COOBn, Me, p -ClC 6 H 4 ; COOEt, COMe, COOEt, p -ClC 6 H 4 ; and others; a = PivCl, base (Et 3 N + DMAP or DBU), MeCN, 20–40 °C, 2–7 days; up to 91% yield.…”

Interrupted Nef Reaction of Cyclic Nitronates: Diastereoselective Access to Densely Substituted α-Chloronitroso Compounds

“…Prepared according to the general procedure from ( E )-1-bromo-2-(2-nitrobut-1-en-1-yl)­benzene (450 mg, 1.76 mmol). Yield: 600 mg (99%).…”

“…-3-ethyl-4,5dihydroisoxazole 2-oxide (1d). Prepared according to the general procedure from (E)-1-bromo-2-(2-nitrobut-1-en-1-yl)benzene 39 General Procedure for the Synthesis of Isoxazoline-Noxides 1g−i. To a stirred solution of nitroalkene (3.0 mmol), benzyldimethylsulfonium bromide 41 (909 mg, 3.9 mmol), and tetrabutylammonium hydrogen sulfate (102 mg, 0.3 mmol) in DCM (6 mL) was added a solution of NaOH (2.04 g, 51 mmol) in water (2.7 mL) at rt.…”