Iron‐Promoted Reductive Ring‐Opening and Isomerization Reactions of C4‐Alkynylisoxazoles Leading to 2‐Alkynylenaminones and Polysubstituted Furans

Abstract

A new iron(III)-promoted reductive ring-opening and isomerization reactions of C4-alkynylisoxazoles in the oxidized N-methylpyrrolidone (NMP*) was reported. By changing the substituents at the C3 and C5 position of the isoxazole ring, the reaction selectively produced 2-alkynylenaminones and polysubstituted furans in good to excellent yields. It was very interesting that large group at the C3 or C5 position of the isoxazole ring was a steric hindrance tertiary butyl group (t-Bu), the reaction proceeded ring-opening rather than isomerization reaction in the presence of FeCl 3 . It was noteworthy that the NMP* as a solvent and a hydrogen donor was essential for both reactions. A plausible mechanism for the reductive ring-opening and isomerization was also proposed. Scheme 2. Fe(III)-promoted isomerization of C4-alkynylisoxazoles 1 a-1 q. [a] Scheme 3. Fe(III)-promoted reductive ring-opening of C4alkynylisoxazoles 1 r-1 u. Scheme 4. Scaled-up experiment of 2 i and 3 s. Scheme 5. Proposed mechanism for ring-opening and isomerization reactions of substrate 1.

Cobalt(II)‐Catalyzed [4+2] Annulation of Picolinamides with Alkynes via C−H Bond Activation

“…Furthermore, the reactions were treated with radical trapping reagents butylated hydroxytoluene (BHT) and 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) under the optimized reaction conditions in parallel. As a result, both BHT and TEMPO had no inhibitory effects on the reactions, which indicating that the radical process should not involve in the alkenylation reaction (Scheme b) . In addition, the Co II ‐catalyzed annulation reaction of picolinamide 1 a and 1,4‐diphenylbutadiyne 4 was performed under the standard reaction conditions, no desired annulation product 3 aa was formed (Scheme c).…”

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).…”

“…Khlebnikov's group has recently reported an iron/gold relay catalyzed isomerization of propargylisoxazoles to pyridines . Our group has also reported an iron‐mediated reductive ring‐opening and isomerization reaction of 4‐alkynylisoxazoles to give furans …”

“…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. We further extended the ring‐opening protocol to 4‐alkynylisoxazole substrates and reported an iron‐catalyzed synthesis of polysubstituted furans . Inspired by these results, we subsequently studied the ring‐opening of 4‐alkenylisoxazoles.…”

Iron Promoted Ring Opening and Ring Closing Cascade (ROCC) Reaction of Ortho‐Carboxy‐Isoxazoles Leading to Isoindolinone Derivatives

“…Isoxazoles have recently emerged as valuable precursors for the synthesis of various other scaffolds [13] . One of the key structural elements of isoxazole which attracts attention of synthetic chemist is the relatively labile N−O bond, which is easy to cleave into heterocyclic compounds [14] .…”