Recent Advances in Copper-Catalyzed Radical C–H Bond Activation Using N–F Reagents

Abstract

This Short Review is aimed at giving an update in the area of copper-catalyzed C–H functionalization involving nitrogen-centered radicals generated from substrates containing N–F bonds. These processes include intermolecular Csp3–H bond functionalization, remote Csp3–H bond functionalization via intramolecular hydrogen atom transfer (HAT), and Csp2–H bond functionalization, which might be of potential use in industrial applications in the future.1 Introduction2 Intermolecular Csp3–H Functionalization3 Remote Csp3–H Functionalization4 Csp2–H Functionalization5 Conclusion

Copper-Catalyzed, N-Directed Distal C(sp3)–H Functionalization toward Azepanes

“…Furthermore, an array of N -fluorosulfonamides could be also accommodated via annulation with 1,3-enyne 5a , thus achieving the desired products ( 6f – j ). Based on the results and previous reports, ,− a plausible mechanism for the [5 + 2] aza-annulation was proposed as depicted in Figure . An in situ formed LCu I species undergoes single-electron-transfer (SET) to N -fluorosulfonamide 1a to give a complex LCu II F, as well as the corresponding nitrogen-centered radical intermediate A .…”

“…Elegant demonstrations of N-radical-mediated remote C­(sp 3 )–H functionalization can be found from the earliest example named the Hofmann–Löffler–Freytag (HLF) reaction for the synthesis of pyrrolidines to the most recent achievements allowing for cross-coupling of the generated alkyl radicals with various nucleophiles via Cu catalysis. − Generally, the classic HLF process occurs by the formation of an unstable N–X (X = Cl, Br, I) bond, followed by N-radical generation and then intramolecular 1,5-hydrogen atom transfer (1,5-HAT), halogenation, and cyclization to afford pyrrolidines (Figure ). The interruption of this process via Cu- or Ni-catalyzed − trapping of the distal alkyl radicals and subsequent cross-coupling could substantially extend the utility of the HLF reaction.…”

Divergent regioselective Heck-type reaction of unactivated alkenes and N-fluoro-sulfonamides

“…The coordination of C=C bond to Cu(I) center would reduce π electron density, and thus activate the olefin moiety. Subsequent SET of Nfluoro-sulfonamide 2a with copper complex I affords amidyl radical II and Cu(II) intermediate III 88 , and the released fluorine anion is proposed to be captured by the protons due to the strong interaction of H-F bond 54,89,90 . The resultant amidyl radical II is a highenergy species 77,91,92 , which undergoes an intramolecular HAT with remote δ-C(sp 3 )−H bond to form a carbon-centered radical IV 93 .…”

Ritter-type amination of C(sp3)-H bonds enabled by electrochemistry with SO42−

“…Meanwhile, the selectivity and reactivity of HAT process can be rationally tuned by varying hydrogen acceptor and reaction additive. For instance, highly selective amination of C(sp 3 )-H bonds has been achieved by employing N -fluorobenzenesulfonimide 10 , 11 , N -hydroxyimide derivatives 12 – 14 and di-tert -butyl peroxide 15 – 17 as HAT agents. Besides, 1,5-HAT enabled by nitrogen-centered radicals has also served as a robust and practical strategy in selective amination of remote unactivated C(sp 3 )-H bonds, especially the classic Hofmann–Löffler–Freytag reaction 18 – 20 .…”