Cu-Catalyzed Direct C–H Alkylation of Polyfluoroarenes via Remote C(sp³)–H Functionalization in Carboxamides

Abstract

A novel dehydrogenative coupling reaction of N-fluorocarboxamides with polyfluoroarenes forming C­(sp2)–C­(sp3) bonds enabled by copper catalysis has been accomplished. N-Fluorocarboxamides are postulated to undergo copper-mediated dehydrogenative cross-coupling reaction with electron-deficient polyfluoroarenes via a radical pathway. Benzylic C–H bonds and aliphatic C–H bonds in N-fluorocarboxamides could proceed smoothly and demonstrated excellent regioselectivity. The detailed mechanism presented is supported by control experiments and density functional theory calculations.

Cu(II)-Catalyzed N-Directed Distal C(sp3)–H Heteroarylation of Aliphatic N-Fluorosulfonamides

“…Recently, our group have successfully realized the regioselective N–F and α-C­(sp 3 )–H arylation of N -fluorosulfonamides with imidazopyridines . Inspired by previous elegant work, ,, we herein report the Cu-catalyzed δ C­(sp 3 )–H heteroarylation of N -fluoroamides via radical-involved 1,5-HAT cascades (Scheme c). A broad range of heteroarenes, including quinoxalinones, quinoline, isoquinoline, 1,4-naphthalenedione, and others, was tolerated in this reaction, which provides a practical strategy for the functionalization of heteroarenes and amides.…”

“…Recently, in-situ-generated amidyls were captured by terminal alkynes to trigger HAT/(3 + 2) or (4 + 2) annulations . Despite the above elegant progress, C­(sp 3 )–H arylation of N -fluoroamides has been less reported and is limited to aryl boronic acid and polyfluoroarenes . Meanwhile, stoichiometric amounts of bases or acids are usually required to successfully access these arylated amides.…”

Site-selective coupling of remote C(sp3)–H/meta-C(sp2)–H bonds enabled by Ru/photoredox dual catalysis and mechanistic studies

“…Therefore, a new methodology that could produce radicals via a new catalytic process rather than through SET with Ru-catalysts would expand the scope of meta -arene C–H bond functionalization reactions, and would provide a new synthetic platform for meta -functionalized arenes. Continuing our research interest in the meta -C(sp 2 )–H bond functionalization reaction 18 and remote C(sp 3 )–H bond activation reaction, 19 here we disclosed a novel example of dual Ru/photoredox-catalyzed meta -alkylation of arenes via site-selective coupling of dual remote C–H bonds, including unactivated γ -C(sp 3 )–H bonds in amides and meta -C(sp 2 )–H bonds in arenes. This reaction represents a novel example of employing a photocatalyst/Ru as a co-catalyst for regioselective CDC of unactivated alkanes and arenes via a new catalytic process, and provides a new strategy to synthesize meta -functionalized arenes under mild reaction conditions ( Scheme 1b ).…”

Chemodivergent Synthesis of Indeno[1,2-b]indoles and Isoindolo[2,1-a]indoles via Mn(III)-Mediated or Electrochemical Intramolecular Radical Cross-Dehydrogenative Coupling

“…Recently, CDC reactions via a radical pathway have emerged as a promising approach toward the synthesis of diverse complex molecules . The advantage of radical CDC is that reactions of radicals can be generated by inexpensive and diversified oxidative processes, including single-electron oxidation by earth-abundant metal complexes (such as Fe, Mn, and Cu); the use of an electric current as a waste-free oxidant; and light-promoted photocatalytic oxidation via single-electron transfer between excited-state photosensitizer and substrate (Scheme ). …”