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

Abstract

The control of regioselectivity in Heck-type reaction of unactivated alkenes represents a longstanding challenge due to several detachable hydrogens in β–H elimination step, which generally afford either one specific regioisomer or a mixture. Herein, a copper-catalyzed intermolecular Heck-type reaction of unactivated alkenes and N-fluoro-sulfonamides with divergent regioselectivities is reported. The complete switch of regioselectivity mainly depends on the choice of different additives. Employment of alcohol solvent gives access to vinyl products, while the addition of carboxylate leads to the formation of allylic products. In addition, exclusion of these two promoting factors results in β-lactams via a C–N reductive elimination. This protocol shows a broad substrate scope for both alkenes and structurally diverse N-fluoro-sulfonamides, producing the corresponding products with excellent regio- and stereoselectivities. Further control experiments and DFT calculations provide in-depth insights into the reaction mechanism, highlighting the distinct effect of the additives on a bidentate auxiliary-stabilized Cu(III) intermediate.

Recent Advances in Theoretical Studies on Cu-Mediated Bond Formation Mechanisms Involving Radicals

“…Spin crossover through an MECP from triplet Int-179 to singlet reductive elimination transition state TS-180 has a free energy barrier of 7.9 kcal/mol (Figure b). A recent study reported by Fu, Guan, and co-workers suggested that a similar reductive elimination ( TS-186 ; Figure b) is also operative in the C–N bond formation of alkyl radical and amide anion, affording a four-membered lactam …”

“…A recent study reported by Fu, Guan, and co-workers suggested that a similar reductive elimination (TS-186; Figure 27b) is also operative in the C−N bond formation of alkyl radical and amide anion, affording a four-membered lactam. 92 4.3. C−O Bond Formation.…”

Rh(III)-Catalyzed Diastereo- and Enantioselective Regiodivergent (Hetero)Arylamidation of (Homo)Allylic Sulfides

“…When employing allylic sulfides as substrates, the challenging 1,2-insertion occurred to afford the Int. I with a locked conformation, wherein β–H elimination was suppressed. Conversely, when homoallylic sulfides are employed, the 2,1-insertion takes place, giving rise to Int.…”

A facile synthesis of α,β-unsaturated imines via palladium-catalyzed dehydrogenation

“…1b). Upon treatment with transition metal (Fe, Cu, Ni) or photocatalysis, the N-fluoroamides can undergo N-F reduction via single-electron transfer (SET) followed by Hofmann-Löffler-Freytag (HLF) type hydrogen atom transfer (HAT) to induce remote C(sp 3 )-H functionalization [70][71][72][73][74][75][76][77][78][79][80] or intramolecular cyclization 81 . Recently, Nagib and co-workers reported a dual photoredox-and copper-catalyzed remote C-H desaturation of N-fluoroamides to furnish δ vinyl amides, that could be converted to diverse families of medicinal motifs 82 .…”