NIS-mediated oxidative cyclization of N-(2-trifluoromethyl-3-alkynyl) hydroxylamines: a facile access to 4-trifluoromethyl-5-acylisoxazoles

Abstract

A novel NIS-mediated oxidative cyclization of N-(2-trifluoromethyl-3-alkynyl)hydroxylamines is developed, which provides a facile access to 4-trifluoromethyl-5-acylisoxazoles in 33-91% yields. Various types of commonly used electrophilic halogen source such as ICl, I2, NIS, NBS and NCS at different temperatures in various solvents were investigated. It was found that the NIS acts as both an oxidant and an electrophile for the present sequential transformation. The scope, mechanism and application of this NIS-mediated domino reaction for further synthetic transformation were studied.

β‐Cyclodextrin–Glycerol Dimers: Synthesis and NMR Conformational Analysis

“…In 2014, in a further extension of this approach, Xiao and Zhang reported the synthesis of 4‐trifluoromethyl‐5‐acylisoxazoles from the corresponding N ‐β‐alkynyl hydroxylamines using NIS as the electrophile (Scheme ) 65. The reaction gives directly the valuable fluorine‐containing isoxazoles from simple starting materials.…”

“… Synthesis of 4‐trifluoromethyl‐5‐acylisoxazoles from N ‐β‐alkynyl hydroxylamines by Xiao and Zhang 65…”

9-Anthraldehyde oxime: a synthetic tool for variable applications

“…Isoxazoles are valuable heterocyclic compounds, playing an outstanding role in many chemical fields and in particular in medicinal chemistry [12]. The isoxazole core can be found in lots of bioactive natural products and pharmaceutical drugs such as valdecoxib, leflunomide, and cloxacillin [13]. Moreover, isoxazole and its derivatives have a wide range of biological activities, for instance as insecticidal, antibacterial, antibiotic, antitumor, antifungal, antituberculosis, anticancer, and ulcerogenic [14,15].…”

N-Halo Reagents: Modern Synthetic Approaches for Heterocyclic Synthesis

“…The oxidative cyclization of N-[2-(trifluoromethyl)alk-3-ynyl]hydroxylamines 271 in the presence of NIS, which acted as both oxidant and electrophile, gave 5-acyl-4-(trifluoromethyl)isoxazoles 272 at room temperature (Scheme 65). 126 The reaction tolerated substitution on the alkyne moiety with aryl, heteroaryl, or cyclopropyl groups. Good yields were obtained for aryl groups containing both electron-donating and electron-withdrawing substituents.…”

“…Limitations were found when the alkyne bearing an TMS group or terminal alkyne were used as substrates. 126…”