A three-component cycloaddition of alkyl trifluorodiazoethane for the synthesis of trifluoromethylated isoxazolines

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

“…In 2017, Zhang, Hu, and co-workers developed a Cu-catalyzed reaction of CF 3 CHN 2 with carboxylic acids and acetonitrile via a similar process to afford a series of N-trifluoroethylimides (Scheme 1b) [40,41]. Inspired by these elegant works [31][32][33][34][35][36][37][38][39][40][41] and based on our continuous interest in reactions of fluoroalkyldiazo compounds [42][43][44][45][46][47][48][49], we sought to develop reactions of the unexplored β-trifluoromethyl β-diazo esters. We hypothesized that nitrile ylides, in situ generated from nitriles and β-trifluoromethyl β-amino esters, could also react with carboxylic acids to give nitriliums, which then could undergo a Mumm rearrangement to provide unsymmetrical β-trifluoromethyl diacyl-β-amino esters as products (Scheme 1c).…”

Energetic Aspects and Molecular Mechanism of 3-Nitro-substituted 2-Isoxazolines Formation via Nitrile N-Oxide [3+2] Cycloaddition: An MEDT Computational Study

“…Isoxazole ring, as well as its hydrogenated analogs (isoxazolines and isoxazolidines), are key molecular segments of many important bioactive structures such as afoxolaner [1], lotilaner [2], sarolaner [3], fenoxasulfone [4], and many others [5][6][7][8][9]. The most universal strategy for the preparation of five-membered heterocycles (including isoxazoles) is [3+2] cycloaddition (32CA) [10][11][12].…”