Radical reactions enabled by polyfluoroaryl fragments: photocatalysis and beyond.

Polyfluoroarenes have been known for a long time, but they are most often used as fluorinated building blocks for the synthesis of aromatic compounds. At the same time, due to peculiar fluorine effect, they have unique properties that provide applications in various fields ranging from synthesis to materials science. This review summarizes advances in the radical chemistry of polyfluoroarenes, which have become possible mainly with the advent of photocatalysis. Transformations of the fluorinated ring via the C-F bond activation, as well as use of fluoroaryl fragments as activating groups and hydrogen atom transfer agents are discussed. The ability of fluoroarenes to serve as catalysts is also considred.

Direct conversion of carboxylic acids to free thiols via radical relay acridine photocatalysis enabled by N-O bond cleavage.

Carboxylic acids and thiols are basic chemical compounds with diverse utility and widespread reactivity. However, the direct conversion of unprotected acids to thiols is hampered due to a fundamental problem - free thiols are incompatible with the alkyl radicals formed on decarboxylation of carboxylic acids. Herein, we describe a concept for the direct photocatalytic thiolation of unprotected acids allowing unprotected thiols and their derivatives to be obtained. The method is based on the application of a thionocarbonate reagent featuring the N-O bond. The reagent serves both for the rapid trapping of alkyl radicals and for the facile regeneration of the acridine-type photocatalyst.

Light-Promoted Dearylation of Perfluorinated Aryl Sulfides with N-Heterocyclic Carbene-Borane.

The removal of the tetrafluoropyridinyl group tethered to a sulfur atom using a complex of N-heterocyclic carbene (NHC) with borane is described. The reaction is performed under blue light irradiation with a disulfide as radical initiator. The selective cleavage of S-Ar in preference to the weaker S-Alk bond is achieved as a result of aromatic radical substitution of the thiyl group by a NHC-stabilized boron-centered radical. Alkyl thiols, which are the primary products of the dearylation, are in situ oxidized or alkylated, affording disulfides or sulfides, respectively.

Photocatalyzed Decarboxylative Thiolation of Carboxylic Acids Enabled by Fluorinated Disulfide.

Thiolation of carboxylic acids using a disulfide reagent having tetrafluoropyridinyl groups is described. The light-mediated process is performed using an acridine-type photocatalyst. Primary, secondary, tertiary, and heteroatom-substituted carboxylic acids can be thiolated, and the method can be applied to the late-stage modification of a range of naturally occurring compounds and drugs. The fluorinated pyridine fragment is believed to enable the C-S bond formation. The resulting sulfides were used as redox-active radical precursors.

Using the Thiyl Radical for Aliphatic Hydrogen-Atom Transfer: Thiolation of Unactivated C-H Bonds.

A metal- and catalyst-free thiyl-radical-mediated activation of alkanes is described. Tetrafluoropyridinyl disulfide is used to perform thiolation of the C-H bonds under irradiation with 400 nm light-emitting diodes. The key C-H activation step is believed to proceed via hydrogen-atom abstraction effected by the fluorinated thiyl radical. Secondary, tertiary, and heteroatom-substituted C-H bonds can be involved in the thiolation reaction. The resulting sulfides have wide potential as photoredox-active radical precursors in reactions with alkenes and heteroarenes.

Fluoroalkyl sulfides as photoredox-active coupling reagents for alkene difunctionalization.

A visible-light-promoted fluoroalkylation-thiolation of alkenes is described. A 4-tetrafluoropyridinylthio fragment serves as a photoredox-active group in the initiation step and undergoes a radical group transfer, which is important for the reaction efficiency. In the primary products, the pyridinylthio substituent may be further functionalized via radical processes or an aromatic substitution reaction.

A novel photoredox-active group for the generation of fluorinated radicals from difluorostyrenes.

A 4-tetrafluoropyridinylthio group was suggested as a new photoredox-active moiety. The group can be directly installed on difluorostyrenes in a single step by the thiolene click reaction. It proceeds upon visible light catalysis with 9-phenylacridine providing various difluorinated sulfides as radical precursors. Single electron reduction of the C-S bond with the formation of fluoroalkyl radicals is enabled by the electron-poor azine ring. The intermediate difluorinated sulfides were involved in a series of photoredox reactions with silyl enol ethers, alkenes, nitrones and an alkenyl trifluoroborate.