Dual Acridine/Decatungstate Photocatalysis for the Decarboxylative Radical Addition of Carboxylic Acids to Azomethines.

A concept for the dual use of acridine and tetrabutylammonium decatungstate photocatalysts in the reactions of carboxylic acids is proposed. Imines generated in situ from aldehydes and p-methoxyaniline, as well as other azomethines, were used as radical acceptors. The role of the decatungstate is believed to facilitate the turnover of the acridine photocatalyst by means of hydrogen atom transfer.

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.

One-Pot Transformation of Aldehydes to Ketones via Minisci-Type Reaction of Imines.

A method for the conversion of aldehydes to ketones via the preliminary formation of aldiminines is described. The imines are involved in acid promoted Minisci-type reaction with alkyl radicals generated from esters of N-hydroxylphthalimide under photoredox conditions. Aminyl radical cations formed after the addition of the iminium ions are believed to be key intermediates, which determine the reaction outcome.

gem-Difluoroolefination of Amides.

A metal-free one-pot process for the gem-difluoroolefination of amides is described. The reaction is based on interaction of generated in situ α-chloroiminium salts with difluorinated phosphorus ylide formed from difluorocarbene and triphenylphosphine. The olefination involves nucleophile-assisted dephosphorylation and proceeds within one hour at low temperature. The gem-difluoroenamines were used in further transformations leading to a variety of fluoroalkylated amines.

C-F Activation of Fluorinated Esters Using Photocatalytically Generated Diaminoalkyl Radical.

A method for hydrofluoroalkylation of alkenes with trifluoroacetic esters under visible light irradiation affording difluorinated products is described. The reaction involves readily available trimethyltriazinane as a shoichiometric reducing agent, which generates a diamino-substituted alkyl radical serving as a strong electron donor. It is believed that the cleavage of the C-F bond by a triazinane-derived radical involves single electron reduction coupled with fluoride transfer.

Dual Photoredox/Copper Catalyzed Fluoroalkylative Alkene Difunctionalization.

A method for performing radical difunctionalization of alkenes using fluorinated halides and a nucleophilic component (thiolate and iodide anions) is described. These nucleophilic fragments serve as redox active groups for performing subsequent transformations. The difunctionalization reaction involves photoredox generation of fluorinated radicals, their addition to the double bond followed by copper-promoted C-S or C-I bond formation. The primary products can be further coupled with silyl enol ethers, α-(trifluoromethyl)styrenes, and trimethylsilyl cyanide affording a variety of fluorinated compounds.

Visible-Light Promoted Radical Fluoroalkylation of O- and N-Substituted Alkenes.

Interaction of enol ethers enol acetates, enamides and enamines with fluorinated reagents may be considered as a reliable method for the synthesis of organofluorine compounds. While classic nucleophile/electrophile substitution or addition mechanisms cannot be realized for coupling of these components, their intrinsic reactivities are revealed with the aid of photoredox catalysis. A combination of these electron donating and accepting components provides a perfect balance needed for individual redox steps, which in some cases may proceed even without a photocatalyst. The same electronic factors also support the key C,C-bond forming event involving addition of fluorinated radical at the electron rich double bond.

Aminals as powerful XAT-reagents: activation of fluorinated alkyl chlorides.

Readily available 1,3,5-trimethyl-1,3,5-triazinane serves as an efficient reagent for halogen atom transfer. Under photocatalytic conditions, the triazinane generates an α-aminoalkyl radical, which can activate the C-Cl bond of fluorinated alkyl chlorides. The hydrofluoroalkylation reaction between fluorinated alkyl chlorides and alkenes is described. The efficiency of the diamino-substituted radical derived from the triazinane is associated with stereoelectronic effects defined by a six-membered cycle forcing the anti-periplanar arrangement of the radical orbital and lone pairs of adjacent nitrogen atoms.

Photoredox Promoted Barbier-Type Reaction of Alkyl Iodides with N-Alkyl and N-Aryl Imines.

The reaction of organozinc reagents with unactivated imines is accelerated when performed in the presence of a photocatalyst under blue light irradiation. Coordination between Lewis acidic zinc iodide and the imine is a key factor responsible for the reaction efficiency. The method can be carried out using alkyl iodides under Barbier conditions.

Organophotoredox-Catalyzed Reductive Tetrafluoroalkylation of Alkenes.

A method for the hydroperfluoroalkylation of alkenes with 1,2-dibromotetrafluoroethane leading to tetrafluorinated bromides is described. The reaction is conveniently performed under blue light irradiation using an organic photocatalyst and ascorbic acid as a reducing agent. Primary products can be further functionalized via radical pathways affording various tetrafluorinated compounds.

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.

Boron Chelates Derived from N-Acylhydrazones as Radical Acceptors: Photocatalyzed Coupling of Hydrazones with Carboxylic Acids.

Difluoroboryl complexes obtained from N-acyl hydrazones upon brief treatment with boron trifluoride and allylic silane serve as efficient acceptors of alkyl radicals. The reaction of the boryl chelates with carboxylic acids in the presence of an acridine-type photocatalyst leading to N-acyl hydrazides is described. The efficiency of addition at the C═N bond of the chelates is determined by the formation of a nitrogen-centered radical stabilized by the boron-containing heterocyclic ring.

Photoredox Activation of Organozinc Reagents: Barbier-Type Reaction of Alkyl Halides with α-(Trifluoromethyl)styrenes.

Organozinc reagents may be activated under blue light irradiation using an organic photocatalyst to generate alkyl radicals. The radicals are trapped by α-(trifluoromethyl)styrenes leading to gem-difluorinated products after elimination of fluoride. The reaction can be conveniently performed under Barbier conditions starting from organic iodides and bromides and elemental zinc.

Synthesis of Difluoroalkylated Heteroarenes via Difluorocarbene.

A diversity-oriented and C2-selective synthesis of difluoroalkyl-substituted heteroarenes from three fragments, N-methoxyazinium salts, difluorocarbene, and electrophilic or radical reagents, is described. The reaction proceeds via the addition of difluorinated phosphorus ylide to in situ methylated heteroarene N-oxides, leading to phosphonium salts, which can undergo further transformations under basic or photoinduced conditions.

Photoredox Catalyzed Dealkylative Aromatic Halogen Substitution with Tertiary Amines.

A reaction of aromatic halides bearing electron-withdrawing groups with tertiary amines in the presence of an iridium catalyst under blue light irradiation is described. Products of the aromatic substitution of the halide by the dialkylamino fragment are obtained. The interaction of aryl radicals with tertiary amines to generate zwitterionic radical species is believed to be the key factor responsible for the reaction efficiency.

All-carbon phosphoranes via difluorocarbene trapping.

A reaction of intramolecularly disposed phosphonium and phenoxide (or thiophenoxide) fragments with difluorocarbene affording all-carbon λ5-phosphoranes is described. The presence of electron-withdrawing CHF2-groups at the phosphonium center is important for the phosphorane formation. In a phosphorane, both phenyl groups located in the equatorial positions undergo 1,2-P,C migration under thermal conditions.

Light-Mediated Sulfur-Boron Exchange.

Interaction of sulfides bearing a tetrafluoropyridinyl group with bis(catecholato)diboron followed by treatment with pinacol and triethylamine affording pinacol boronic esters is described. The reaction is promoted by an organic photocatalyst (3DPA2FBN) under irradiation with 400 nm light, and works with primary, secondary, and tertiary sulfides. The electron depleting character of the fluorinated pyridine fragment plays an important role in generating alkyl radicals.

Atom-transfer radical addition of fluoroalkyl bromides to alkenes via a photoredox/copper catalytic system.

A method for the addition of fluorinated alkyl bromides to alkenes is described. The reaction proceeds under visible light irradiation in the presence of two catalysts: Ir(ppy)3 and N-heterocyclic carbene ligated copper bromide (IMesCuBr). The role of the iridium photocatalyst is to generate the fluoralkyl radical, while the copper promotes formation of the carbon-bromine bond.