Synthesis of β‐Isoxazole Carbonyl Derivatives and their Analogues via Palladium‐Catalyzed Sequential C(sp²)−O/C(sp²)−C(sp³) Bond Formations

Abstract

An efficient Pd(II)‐catalyzed one‐pot tandem cyclization/alkylation reaction of internal alkynes has been reported. In this reaction, a wide range of structurally diverse β/;‐isoxazole aldehydes/ketones could be obtained in good to excellent yields from various alkynyl oxime ethers and allylic or homoallylic alcohols. The gram‐scale experiment and various transformations of the newly obtained products demonstrated that this method should be a general and useful synthetic tool.magnified image

Palladium‐Catalyzed Cascade Cyclization/Alkylation of Oxime Ethers: Assembly of 4‐Alkylisoxazoles by “Chain‐Walking” Strategy

“…On the basis of the obtained experimental results and previous relevant reports, [19a,20b,21b,23] a tentative reaction mechanism involving chain walking process is proposed (Scheme 5). In the presence of excess bromine ions, oxypalladation of alkynone O ‐methyloximes 1 gives vinyl palladium species I , [19a] followed by migration of alkene 2 to afford alkyl‐palladium species II [23b] . Subsequently, intermediate II undergoes consecutive β ‐hydride elimination and coordination of HPdX species generates the intermediate III [3b,24] .…”

A review of recent synthetic strategies and biological activities of isoxazole

“…In (Scheme 40) shows a one‐pot tandem Pd(II)‐catalyzed cyclization/alkylation process of internal alkynes [61]. Several alkynyl oxime ethers 1 and allylic or homoallylic alcohols 2 were used in this reaction to produce a wide range of structurally varied ß\ɷ‐ isoxazole aldehydes/ketones 3 in good to outstanding yields.…”

“…The 3-amino-5-(methyl/t-butyl)isoxazoles 1 were utilized as key starting materials for the synthesis of the new compounds. The isoxazole-thiazolone derivatives 2 were synthesized by heating compound 1 with S C H E M E 4 0 Synthesis of diverse ß/ ɷ-isoxazole aldehydes/ketones derivatives [61] S C H E M E 4 1 Synthesis of isoxazole under TEMPO-catalyzed aerobic conditions [62] S C H E M E 4 2 Synthesis of 3, 5-(bis)isoxazole via intramolecular N-O bond formation [63] S C H E M E 4 3 An intramolecular Wittig approach for the synthesis of isoxazoles [64] S C H E M E 4 4 An intramolecular cyclization approach for the synthesis of isoxazoles [65] ammonium thiocyanate in refluxing ethanol. The reaction of 2 with aromatic aldehydes in presence of an ethanolic solution of sodium hydroxide gave the corresponding 5-arylidenethiazolone-isoxazole derivatives 3 as depicted in Scheme 49.…”

Pd-Catalyzed Sequential Electrophilic Cyclization/Selective C–H Annulation Cascade: Synthesis of Isoxazole-Phthalimide-Fused Poly-Heterocyclics

“…For instance, Chen and co-workers revealed a cascade cyclization/alkenylation with activated alkenes (Scheme b) . Alkynes were also coupled in tandem in a similar manner (Scheme c) by Jiang et al The same group later reported an interesting redox coupling of allyl alcohols to construct 4-alkylated isoxazoles (Scheme d) …”

“…10 Alkynes were also coupled in tandem in a similar manner (Scheme 1c) 11 by Jiang et al The same group later reported an interesting redox coupling of allyl alcohols to construct 4alkylated isoxazoles (Scheme 1d). 12 Surprisingly, the incipient alkenyl-palladium intermediate could not be molded for successive activation of C−H bonds in spite of its availability at a reachable distance on both sides (Scheme 1e, Ar 1 & Ar 2 ). With our persistent interest in the combined alkyne/C−H activation, 13 we herein reveal the tactic of annulating maleimides in succession to isoxazole formation by successfully transporting the Pd center from C-4 to the C− H bond of arene.…”