Photoredox-catalyzed C-C bond cleavage of cyclopropanes for the formation of C(sp3)-heteroatom bonds.

Sterically congested C-O and C-N bonds are ubiquitous in natural products, pharmaceuticals, and bioactive compounds. However, the development of a general method for the efficient construction of those sterically demanding covalent bonds still remains a formidable challenge. Herein, a photoredox-driven ring-opening C(sp3)-heteroatom bond formation of arylcyclopropanes is presented, which enables the construction of structurally diversified while sterically congested dialkyl ether, alkyl ester, alcohol, amine, chloride/fluoride, azide and also thiocyanate derivatives. The selective single electron oxidation of aryl motif associated with the thermodynamic driving force from ring strain-release is the key for this transformation. By this synergistic activation mode, C-C bond cleavage of otherwise inert cyclopropane framework is successfully unlocked. Further mechanistic and computational studies disclose a complete stereoinversion upon nucleophilic attack, thus proving a concerted SN2-type ring-opening functionalization manifold, while the regioselectivity is subjected to an orbital control scenario.

Visible-Light-Promoted Regioselective 1,3-Fluoroallylation of gem-Difluorocyclopropanes.

A strategically novel protocol for ring-opening functionalization of aryl gem-difluorocyclopropanes (F2CPs), which allows an expedient construction of CF3-containing architectures via visible-light-promoted F-nucleophilic attack manifold, was disclosed. Single electron oxidation of F2CPs was ascribed as the critical step for the success of this transformation by prompting F-nucleophilic attack, as well as the ensuing C-C bond scission. The observed intriguing regioselectivity for fluoroincorporation in this reaction was rationalized by invoking the cation-stabilization property of gem-difluorine substituents and also the thermodynamic gains acquired from forming CF3 functionality. By using cost-effective fluorination reagent and readily available substrates, a broad collection of structurally diversified α-allyl-ß-trifluoromethyl ethylbenzene derivatives could be obtained in generally good yields. Further mechanistic investigations proved the engagement of a benzylic radical intermediate in this transformation.

Photoredox-catalyzed oxo-amination of aryl cyclopropanes.

Cyclopropanes represent a class of versatile building blocks in modern organic synthesis. While the release of ring strain offers a thermodynamic driving force, the control of selectivity for C-C bond cleavage and the subsequent regiochemistry of the functionalization remains difficult, especially for unactivated cyclopropanes. Here we report a photoredox-coupled ring-opening oxo-amination of electronically unbiased cyclopropanes, which enables the expedient construction of a host of structurally diverse ß-amino ketone derivatives. Through one electron oxidation, the relatively inert aryl cyclopropanes are readily converted into reactive radical cation intermediates, which in turn participate in the ensuing ring-opening functionalizations. Based on mechanistic studies, the present oxo-amination is proposed to proceed through an SN2-like nucleophilic attack/ring-opening manifold. This protocol features wide substrate scope, mild reaction conditions, and use of dioxygen as an oxidant both for catalyst regeneration and oxygen-incorporation. Moreover, a one-pot formal aminoacylation of olefins is described through a sequential cyclopropanation/oxo-amination.

Photoredox-Coupled F-Nucleophilic Addition: Allylation of gem-Difluoroalkenes.

A novel strategy for the expedient construction of CF3 -embeded tertiary/quarternary carbon centers was developed by taking advantage of photoredox catalysis. Thanks to a key step of single-electron oxidation, electron-rich gem-difluoroalkenes, which otherwise are essentially reluctant towards F-nucleoplilic addition, now readily participate in this fluoroallylation reaction. Furthermore, this strategy provides an elegant example for the generation, as well as functionalization, of α-CF3 -substituted benzylic radical intermediates using cheap and readily available starting materials.

Photoredox Catalysis Induced Bisindolylation of Ethers/Alcohols via Sequential C-H and C-O Bond Cleavage.

A visible-light-engaged 2-fold site-selective alkylation of indole derivatives with aliphatic ethers or alcohols has been accomplished for easy access to symmetric 3,3'-bisindolylmethane derivatives. The experimental data suggest a sequential photoredox catalysis induced radical addition and proton-mediated Friedel-Crafts alkylation mechanism.

Nonconventional difluoroalkylation of C(sp2)-H bonds through hydroarylation.

An unprecedented Rh-catalyzed C2-difluoroalkylation of indole derivatives with 2,2-difluorovinyl arenesulfonates has been reported. This reaction provides a rare instance of catalytic difluoroalkylation through hydroarylation of gem-difluoroalkenes. The sulfonate group works as a chelating ligand, thus stabilizing the rhodacycle intermediate, leading to the uncommon transformation.

Manganese-catalyzed synthesis of monofluoroalkenes via C-H activation and C-F cleavage.

The manganese-catalyzed α-fluoroalkenylation of arenes via C-H activation and C-F cleavage has been described. This protocol provides a very useful method for the synthesis of monofluoroalkenes with predominant unconventional E-isomer selectivity which complements the existing strategies for the access to these molecular architectures. In addition, the selectivity of ß-defluorination in the catalytic cycle not only determines the configurations of the products but also obviates the use of external oxidants, providing a good example in the exploitation of manganese-catalyzed redox-neutral C-H transformations.