Iron-Catalyzed Transfer Hydrogenation in Aged N-Methyl-2-pyrrolidone: Reductive Ring-Opening of 3,5-Disubstituted Isoxazoles and Isoxazolines

Abstract

3,5-Disubstituted isoxazoles and isoxazolines undergo an iron-catalyzed reductive ring-opening in aged N-methyl-2-pyrrolidone (NMP). 5-Hydroxy-N-methyl-2-pyrrolidone generated in situ via a simple activation of commercial NMP acts as the hydrogen donor in the iron-catalyzed transfer hydrogenation reaction. It is the first example employing a combination of an iron catalyst and 5-hydroxy-N-methyl-2-pyrrolidone as reducing agents in a transfer hydrogenation reaction. The protocol is highly efficient for the synthesis of β-enaminones and 1,3-diketones, providing a versatile route for the preparation of these 1,3-difunctional compounds bearing diversified substitution patterns.

Iron‐Mediated Ring‐Opening and Rearrangement Cascade Synthesis of Polysubstituted Pyrroles from 4‐Alkenylisoxazoles

“…2,3,5‐Trisubstituted pyrrole 2 a was obtained in 62% yield after 15 hours (Table , entry 1). Further experimental data revealed that the ring‐opening of 4‐alkenylisoxazole 1 a did not depend on the aged NMP solvent, unlike the previous iron‐catalyzed reductive ring‐opening of 3,5‐disubstituted isoxazole reaction or the ring‐opening of 4‐alkynylisoxazoles to polysubstituted furans . Substrate 1 a reacted smoothly in non‐activated NMP solvent and afforded the same rearrangement product 2 a in 68% yield (Table , entry 2).…”

“…A series of 4‐alkenylisoxazoles 1 were synthesized by a palladium‐catalyzed cascade cyclization‐alkenylation protocol previously reported by our group . We chose ( E )‐3‐( tert ‐butyl)‐5‐phenyl‐4‐styrylisoxazole 1 a as the model substrate for reaction condition optimization, and first employed the conditions reported in our previous iron‐catalyzed reductive ring‐opening of 3,5‐disubstituted isoxazoles . To our delight, a ring‐opening and rearrangement cascade took place smoothly in the presence of 0.15 equiv.…”

“…We, therefore, investigated the transition‐metal‐catalyzed ring‐opening of isoxazoles and reported an iron‐catalyzed reductive ring‐opening of 3,5‐disubstituted isoxazoles and isoxazolines to β ‐enaminones . It was found to be a transfer hydrogenation reaction, taking place in aged NMP, and 5‐hydroxy‐NMP generated in the aged solvent acted as the hydrogen donor.…”

TEMPO‐Mediated Selective Synthesis of Isoxazolines, 5‐Hydroxy‐2‐isoxazolines, and Isoxazoles via Aliphatic δ‐C(sp3)‐H Bond Oxidation of Oximes

“…Thus, these scaffolds could take part in hydrogen bonds, donor‐acceptor interactions with various enzymes and receptors [6] . Currently, various life‐saving drugs contain isoxazoles and isoxazolines moieties (Figure 1A) [7] and 5‐hydroxy‐2‐isoxazolines have been utilized as a versatile synthon possibly because it can be easily transformed into various functional groups like isoxazoles, β ‐enaminones, 1,3‐diketones, γ ‐amino alcohols, and N ‐aryl‐ β ‐lactams, etc [8–10] . Isoxazoles are also extensively used as 1,3‐dicarbonyl equivalents in natural product synthesis [11] .…”

Diversity-Oriented Synthesis of Highly Functionalized Alicycles across Dipolar Cycloaddition/Metathesis Reaction

“…The synthesis of highly functionalized cyclopentane derivatives gained considerable attention in medicinal chemistry, as a result of their various biological activities. [15][16][17][18][19][20][21][22][23][24] Some isoxazoline derivatives were earlier synthesized starting from various cyclic -amino acids by applying regio-and stereoselective 1,3-dipolar cycloaddition of nitrile oxide. [24][25][26][27][28][29] Moreover, cyclic -amino This document was downloaded for personal use only.…”