Photoredox Generation of Isothiouronyl Radical Cations: A New Platform in Covalent Radical Catalysis

Abstract

Thiyl radicals offer unique catalytic patterns for the direct covalent activation of alkenes. However, important limitations in terms of structural diversity and handling have hampered the routine use of thiyl radicals in covalent radical catalysis. Herein, we report a new class of cationic sulfur-centered radicals to achieve covalent radical catalysis. Their generation from highly modular thioureas by photoredox catalysis make their utilization very simple and reliable. The synthetic potential and the versatility of the catalytic system were finally evaluated in a (3+2)-radical cascade between vinylcyclopropanes and olefins.

Formal Cycloadditions Driven by the Homolytic Opening of Strained, Saturated Ring Systems

“…Isothiouronyl radical cations are also effective catalysts for vinylcyclopropane/alkene FCA. [47] While most cyclopropane substrates studied bore the privileged dicarbonyl motif, several more medchem-relevant examples were reported. For example, reaction of 1-vinyl-2,2-difluorocyclopropane with N-vinylacetamide gave 90 b in 71 % yield.…”

Palladium-catalysed enantio- and regioselective (3 + 2) cycloaddition reactions of sulfamidate imine-derived 1-azadienes towards spirocyclic cyclopentanes

“…[1][2][3] Due to their importance, synthetic protocols enabling efficient access to this privileged motif with high stereocontrol are indispensable and highly sought aer. Among these, a commonly employed strategy concerns the use of donor-acceptor cyclopropanes (DACs) as C3 synthons in (3 + 2) cycloaddditions, which allow the effective construction of these ve-membered carbocycles [4][5][6][7][8] as well as their heterocyclic counterparts [9][10][11][12][13] in a stereoselective and atom economical fashion. Within the array of structurally diverse DACs lies the vinylcyclopropane (VCP) scaffold, which readily ring-open in the presence of a transition metal catalyst such as palladium to afford a metal-bound zwitterionic p-allyl dipole that can undergo (3 + 2) cycloaddition with an array of dipolarophiles to furnish ve-membered rings bearing a synthetically valuable vinyl handle.…”

Thiol-Catalyzed Photodriven Stereoselective Hydrodifluoroacetylative Cyclization of Alkyne

“…The incipient research has disclosed that thiol possesses the capability of rapidly transferring a hydrogen atom to most types of radicals X• having an X–H bond dissociation energy (BDE) higher than that of an S–H bond. − Although most of the reported photoredox reactions using thiol or disulfide precatalysts exploited the specialty of thiyl radical in affording various carbon-centered radical intermediates with good stereoselectivity, − the potential of such a thiol catalyst in enhancing reactivity and stereoselectivity during the HAT process has yet to be explored. − Herein, we report a photodriven stereoselective intramolecular hydrodifluoroacetylation of internal alkyne by the utilization of a thiol catalyst (Figure c). A mechanistic investigation was conducted to elucidate the advantage of a sterically hindered thiol-mediated HAT process in promoting stereoselectivity and reactivity.…”