Palladium-Catalyzed Cascade Annulation/Allylation of Alkynyl Oxime Ethers with Allyl Halides: Rapid Access to Fully Substituted Isoxazoles

Abstract

A novel and efficient approach for the synthesis of functionalized isoxazoles via palladium-catalyzed cascade annulation/allylation of alkynyl oxime ethers with allyl halides has been established. The present protocol exhibits mild reaction conditions, good functional group compatibility, and convenient operation. Moreover, scalability was performed and further decoration of the isoxazole product was achieved.

Synthesis of 4‐Chalcogenylated Isoxazoles Mediated by PhICl2 and Diorganyl Disulfides/Diselenides

“…The substrates alkynone Z ‐ O ‐methyloximes were synthesized according to the literatures [22a] . 1 a – c , 1 h – j , 1 l – p are known compounds and their NMR data are in agreement with those reported in the literatures [10a,17a,20,23] .…”

Recent advances in metal catalyzed or mediated cyclization/functionalization of alkynes to construct isoxazoles

“…Furthermore, by using a similar cascade cyclization/ functionalization synthetic tactics, our group developed a palladium-catalyzed cascade annulation/allylation of alkynone O-methyloximes (19) with allyl halides (20) for the rapid construction of fully substituted isoxazole derivatives (21) (Scheme 9). 27 Using 3 mol% of Pd(OAc) 2 as the catalyst and 1 equiv. nBuN 4 Br as the additive in DMF at 80°C for 5-40 min, both aromatic and aliphatic alkynone O-methyloximes (19) with different functional groups were smoothly transformed into the desired products in good to excellent yields with high regioselectivities.…”

“…In a subsequent study, 4-sulfenylisoxazole derivatives (27) were efficiently assembled through a palladium-catalyzed three component cascade annulation/sulfenylation using readily available Na 2 S 2 O 3 as an odorless sulfenylation reagent (Scheme 12). 31 In this transformation, one C-O bond and two C-S bonds were formed in the cascade process.…”

Copper(II)-Catalyzed Domino Synthesis of 4-Benzenesulfonyl Isoxazoles from 2-Nitro-1,3-enynes, Amines, and Sodium Benzenesulfinate

“…13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 174.0, 162. 5,145.1,141.3,141.1,138.2,133.5,132.1,129.8,128.9,128.8,128.5,128.2,127.8,126.6,125.3,122.5,120.7 (q,J = 255.4 Hz),117.3,114.3,54.2. 19 2-Methyl-N-(phenyl (5-phenyl-4-(phenylsulfonyl)isoxazol-3-yl)methyl)aniline 4p.…”

“…Since Claisen first discovered the method to synthesize isoxazoles, 2 many alternate routes for acquiring synthetic isoxazoles have been reported. These approaches can be summarized as the following four major types: (i) 1,3-dipolar cycloaddition, 3 (ii) condensation reactions of 1,3-dicarbonyl derivatives, 4 (iii) cycloisomerization, 5 and (iv) intramolecular addition of nitro group to unsaturated carbon−carbon bonds. 6 Wang and coworkers described the synthesis of isoxazoles from alkynes and nitroalkanes (Scheme 1a).…”