A three-component synthesis of aryl(heteroaryl)acylamides

Abstract

A three-component reaction of azole or azine N-oxides, 1,1-difluorostyrenes and amines gives amides of α-aryl-α-heteroarylacetic or propionic acids. The key step is 1,3-dipolar cycloaddition between N-oxide and difluorostyrene leading to the acyl fluoride intermediate, which has been identified and characterized by NMR spectroscopy. The whole process is an example of selective functionalization of C-H bonds in both 5- and 6-membered heterocyclic systems.

An I(I)/I(III) Catalysis Route to the Heptafluoroisopropyl Group: A Privileged Module in Contemporary Agrochemistry

“…19 F NMR (376 MHz, Chloroform-d) δ -59.3 (dd, J = 24.2, 11.1 Hz), -76.1 (qd, J = 24.2, 12.7 Hz), -77.9 --78.1 (m, J = 11.4 Hz). HRMS (EI): m/z [M] + calcd for C13H13F5 + : 264.09319; found: 264.09317.Analytical data in agreement with the literature data 37.…”

Recent Advances in Cycloaddition Reactions of Heterocyclic N-Oxides

“…Tetrasubstituted 1,1-difluorostyrenes provide imidazoles with all-carbon quaternary centers (including CF 3 -substituted ones) connected to the heterocyclic ring, although in lower yields than trisubstituted substrates. According to expectation, a monofluorostyrene gives an aryl(heteroaryl)acetaldehyde in the reaction with quinoline N-oxide derivative, but it reacts much more sluggishly than difluorostyrenes [95]. The mechanism of cycloaddition of N-oxides with difluorostyrenes is probably similar to the one discussed for perfluoroalkenes.…”

“…This compound has been observed and characterized by NMR spectroscopy as the sole product when an imidazole N-oxide derivative and 2-arylpentafluoropropene were mixed in deuterated THF at 70 C [95]. When p-toluidine was added to the reaction mixture prepared in a similar manner, the expected amide was obtained in good yield (Scheme 20).…”

“…The quinoline-derived product shows preference for the exomethylene tautomeric structure. Amides of 2-heteroarylacetic acids can be assembled in a one-pot, three-component reaction of N-oxides, difluorostyrenes, and various amines (Scheme 19) [95]. Difluorostyrenes are much less electrophilic than HFP or PFP; thus there is usually no need to separate the two steps of the reaction, that is, acyl fluorideforming 1,3-cycloaddition and reaction with nucleophile.…”

Recent Progress in Non‐Catalytic C–H Functionalization of Heterocyclic N‐Oxides

“…A large number of various derivatives of azines and azoles are produced by the approach consistently developed in the works of Loska, [82][83][84][85][86] based on the interaction of their N-oxides with fluorolefins.…”