The application of abundant and inexpensive fluorine feedstock sources to synthesize fluorinated compounds is an appealing yet underexplored strategy. Here, we report a photocatalytic radical hydrodifluoromethylation of unactivated alkenes with an inexpensive industrial chemical, chlorodifluoromethane (ClCF2H, Freon-22). This protocol is realized by merging tertiary amine-ligated boryl radical-induced halogen atom transfer (XAT) with organophotoredox catalysis under blue light irradiation. A broad scope of readily accessible alkenes featuring a variety of functional groups and drug and natural product moieties could be selectively difluoromethylated with good efficiency in a metal-free manner. Combined experimental and computational studies suggest that the key XAT process of ClCF2H is both thermodynamically and kinetically favored over the hydrogen atom transfer pathway owing to the formation of a strong boron-chlorine (B-Cl) bond and the low-lying antibonding orbital of the carbon-chlorine (C-Cl) bond.

Difluoromethylation of Unactivated Alkenes Using Freon-22 through Tertiary Amine-Borane-Triggered Halogen Atom Transfer.

In recent years, remarkable advances on remote C(sp3)-H bond or aldehydic C(sp2)-H functionalizations enabled by intermolecular radical addition to C=C bond/(1,n)-HAT tandem sequences have been witnessed, which provided an efficient...

Radical Addition to C=C Bond Meets (1,n)-HAT: Recent Advances on Remote C(sp3)-H or C(sp2)-H Functionalization of Alkenes

The combination of visible light irradiation and Pd-catalysis has been practically employed for the C-H alkylation reactions of naphthylamines and α-diazo esters, leading to the synthesis of α-naphthyl functionalized acetates via C-C bond construction under mild reaction conditions and under solvent-free conditions. The light irradiation has been proven to play a pivotal role in the reactions, probably by promoting the generation of active carbene species from α-diazo esters.

Synergistic Visible Light and Pd-Catalyzed C-H Alkylation of 1-Naphthylamines with α-Diazoesters.

Photoredox Catalytic Cascade Radical Addition to Construct 1,4- Diketone-Functionalized Quinoxalin-2(1H)-one Derivatives

Radical transformations are powerful in organic synthesis for the construction of molecular scaffolds and introduction of functional groups. In radical difunctionalization reactions, the radicals in the first functionalized intermediates can be relocated through resonance, hydrogen atom or group transfer, and ring opening. The resulting radical intermediates can undertake the following paths for the second functionalization: (1) couple with other radical groups, (2) oxidize to cations and then react with nucleophiles, (3) reduce to anions and then react with electrophiles, (4) couple with metal-complexes. The rearrangements of radicals provide the opportunity for the synthesis of 1,3-, 1,4-, 1,5-, 1,6-, and 1,7-difunctionalization products. Multiple ways to initiate the radical reaction coupling with intermediate radical rearrangements make the radical reactions good for difunctionalization at the remote positions. These reactions offer the advantages of synthetic efficiency, operation simplicity, and product diversity.

https://www.mdpi.com/1420-3049/28/7/3027/pdf?version=1680075096

Remote Radical 1,3-, 1,4-, 1,5-, 1,6- and 1,7-Difunctionalization Reactions

Photoredox-Catalyzed Synthesis of Remote Fluoroalkylated Azaarene Derivatives and the α-Deuterated Analogues via 1,n-Hydrogen-Atom-Transfer-Involving Radical Reactions.

Wenhui Wei

Papers

Photoredox-Catalyzed Synthesis of Remote Fluoroalkylated Azaarene Derivatives and the α-Deuterated Analogues via 1,n-Hydrogen-Atom-Transfer-Involving Radical Reactions.