Hydrogen Atom Transfer Catalyst Research Articles

Visible-Light Photocatalysis of Eosin Y: HAT and Complementing MS-CPET Strategy to Trifluoromethylation of β-Ketodithioesters with Langlois' Reagent.

A metal- and oxidant-free photoinduced strategy for thioxo sulfur-selective trifluoromethylation of β-ketodithioesters at room temperature is reported. Excellent Z/E-stereoselectivity has been achieved with cheap and viable Langlois' reagent (CF3SO2Na, sodium triflinate) in the presence of eosin Y, which acts as a hydrogen atom transfer (HAT) catalyst. The reaction proceeds via disulfide intermediate disulfanediylbis(3-(alkylthio)-1-phenylprop-2-en-1-one) (a dimer of β-ketodithioester) followed by complementing proton-coupled electron transfer-mediated reverse HAT cycle of eosin Y. This operationally simple and efficient protocol allows direct access to triflinated α-oxoketene dithioacetals in good to excellent yields bearing diverse synthetically useful functional groups of different electronic and steric nature.

An overview on disulfide-catalyzed and -cocatalyzed photoreactions.

Disulfides are versatile catalysts. They can be photocatalysts, hydrogen atom transfer (HAT) catalysts, cocatalysts, or initiators in photocatalytic reactions. Under photoirradiation, organic disulfides can be easily cleaved into free thiyl radicals (RS•) and can reversibly add to unsaturated multiple bonds to catalyze a variety of functionalization reactions under mild conditions. In photoredox catalysis reactions, an excellent electron transfer ability and excellent radical properties also made these thiyl radicals powerful HAT catalysts. They have increasingly been proven useful in various types of organic photoreactions, such as cyclizations, anti-Markovnikov additions, aromatic olefin carbonylations, isomerizations, etc. They are a class of green, economic, mild, and chemoselective radical catalysts that deserve more attention. The present review highlights the recent progress in the field of disulfide-catalyzed and -cocatalyzed photocatalytic reactions for different reaction types.

Photocatalytic α-Tertiary Amine Synthesis via C-H Alkylation of Unmasked Primary Amines.

A practical, catalytic entry to α,α,α‐trisubstituted (α‐tertiary) primary amines by C−H functionalisation has long been recognised as a critical gap in the synthetic toolbox. We report a simple and scalable solution to this problem that does not require any in situ protection of the amino group and proceeds with 100 % atom‐economy. Our strategy, which uses an organic photocatalyst in combination with azide ion as a hydrogen atom transfer (HAT) catalyst, provides a direct synthesis of α‐tertiary amines, or their corresponding γ‐lactams. We anticipate that this methodology will inspire new retrosynthetic disconnections for substituted amine derivatives in organic synthesis, and particularly for challenging α‐tertiary primary amines.

Photocatalytic α‐Tertiary Amine Synthesis via C−H Alkylation of Unmasked Primary Amines

AbstractA practical, catalytic entry to α,α,α‐trisubstituted (α‐tertiary) primary amines by C−H functionalisation has long been recognised as a critical gap in the synthetic toolbox. We report a simple and scalable solution to this problem that does not require any in situ protection of the amino group and proceeds with 100 % atom‐economy. Our strategy, which uses an organic photocatalyst in combination with azide ion as a hydrogen atom transfer (HAT) catalyst, provides a direct synthesis of α‐tertiary amines, or their corresponding γ‐lactams. We anticipate that this methodology will inspire new retrosynthetic disconnections for substituted amine derivatives in organic synthesis, and particularly for challenging α‐tertiary primary amines.

A Bond-Weakening Borinate Catalyst that Improves the Scope of the Photoredox α-C–H Alkylation of Alcohols

The development of catalyst-controlled, site-selective C(sp3)–H functionalization reactions is currently a major challenge in organic synthesis. In this paper, a novel bond-weakening catalyst that recognizes the hydroxy group of alcohols through formation of a borate is described. An electron-deficient borinic acid–ethanolamine complex enhances the chemical yield of the α-C–H alkylation of alcohols when used in conjunction with a photoredox catalyst and a hydrogen atom transfer catalyst under irradiation with visible light. This ternary hybrid catalyst system can, for example, be applied to functional-group-enriched­ peptides.

Light-Mediated Asymmetric Aliphatic C–H Alkylation with Hydrogen Atom Transfer Catalyst and Chiral Phosphoric Acid

In the presence of tetrabutylammonium decatungstate and chiral spiro phosphoric acid, a light-mediated asymmetric C–H functionalization of unactivated hydrocarbons with exocyclic enones has been es...

Visible‐Light‐Induced Selective Defluoroborylation of Polyfluoroarenes, gem‐Difluoroalkenes, and Trifluoromethylalkenes

AbstractFluorinated organoboranes serve as versatile synthetic precursors for the preparation of value‐added fluorinated organic compounds. Recent progress has been mainly focused on the transition‐metal catalyzed defluoroborylation. Herein, we report a photocatalytic defluoroborylation platform through direct B−H activation of N‐heterocyclic carbene boranes, through the synergistic merger of a photoredox catalyst and a hydrogen atom transfer catalyst. This atom‐economic and operationally simple protocol has enabled defluoroborylation of an extremely broad scope of multifluorinated substrates including polyfluoroarenes, gem‐difluoroalkenes, and trifluoromethylalkenes in a highly selective fashion. Intriguingly, the defluoroborylation protocol can be transition‐metal free, and the regioselectivity obtained is complementary to the reported transition‐metal‐catalysis in many cases.

Visible-Light-Induced Selective Defluoroborylation of Polyfluoroarenes, gem-Difluoroalkenes, and Trifluoromethylalkenes.

Fluorinated organoboranes serve as versatile synthetic precursors for the preparation of value-added fluorinated organic compounds. Recent progress has been mainly focused on the transition-metal catalyzed defluoroborylation. Herein, we report a photocatalytic defluoroborylation platform through direct B-H activation of N-heterocyclic carbene boranes, through the synergistic merger of a photoredox catalyst and a hydrogen atom transfer catalyst. This atom-economic and operationally simple protocol has enabled defluoroborylation of an extremely broad scope of multifluorinated substrates including polyfluoroarenes, gem-difluoroalkenes, and trifluoromethylalkenes in a highly selective fashion. Intriguingly, the defluoroborylation protocol can be transition-metal free, and the regioselectivity obtained is complementary to the reported transition-metal-catalysis in many cases.

Photoactive Metal-Organic Framework for the Reduction of Aryl Halides by the Synergistic Effect of Consecutive Photoinduced Electron-Transfer and Hydrogen-Atom-Transfer Processes.

Consecutive photoinduced electron transfer (ConPET) has advantages on overcoming the current energetic limitation of visible-light photoredox catalysis for utilizing the energies of two photons in one catalytic cycle. A heterogeneous approach for radical chain reduction of various aryl bromides and chlorides without adding any cocatalyst is introduced by incorporating polyoxometalates (POMs) and amine catalysts into a naphthalenediimide (NDI)-based polymer. CoW-DPNDI-PYI exhibits high activity in the photocatalytic reduction of aryl halides by the synergistic effects of ConPET and hydrogen-atom-transfer (HAT) processes and an enzyme-mimicking CO2 cycloaddition reaction. The ConPET process with N,N'-bis(4-pyridylmethyl)naphthalenediimide (DPNDI) facilitates effective solar energy conversion. POMs and amine catalysts, as efficient HAT catalysts and electron donors, improve the generation of the ConPET process. The success of this work demonstrates the great application of the synergistic effects of ConPET and HAT processes in heterogeneous photocatalysis C-H arylation.

Identification of Bond‐Weakening Spirosilane Catalyst for Photoredox α‐C−H Alkylation of Alcohols

AbstractThe development of catalyst‐controlled site‐selective C(sp3)−H functionalization is a current major challenge in organic synthesis. This paper describes DFT‐guided identification of pentavalent silicate species as a novel bond‐weakening catalyst for the α‐C−H bonds of alcohols together with a photoredox catalyst and a hydrogen atom transfer catalyst. Specifically, Martin's spirosilane accelerated α‐C−H alkylation of alcohols.magnified image

Zwitterionic 1,2,3-Triazolium Amidate as a Catalyst for Photoinduced Hydrogen-Atom Transfer Radical Alkylation

A zwitterionic 1,2,3-triazolium amidate was designed for use as an effective modular hydrogen-atom transfer catalyst for photoredox C–H functionalization. This zwitterionic amidate is stable yet am...

Implementing Hydrogen Atom Transfer (HAT) Catalysis for Rapid and Selective Reductive Photoredox Transformations in Continuous Flow

The reductive transformation of aryl halides and carbonyl compounds is a key step in many photoredox transformations. By combining a highly reducing organic photocatalyst with a thiol hydrogen atom transfer (HAT) catalyst, we showcase rapid and highly selective reactions of these synthetically important starting materials in continuous flow. The fast reduction of aryl iodides, bromides and chlorides has been demonstrated with residence times in some cases below one minute. Selectivity between mono‐ and di‐dehalogenation could also be achieved in some cases. Aryl ketones, aldehydes and imines were shown to undergo facile pinacol couplings, and the coupling of an aryl chloride with a styrene was also successful.

Photocarboxylation of Benzylic C-H Bonds.

The carboxylation of sp3-hybridized C–H bonds with CO2 is a challenging transformation. Herein, we report a visible-light-mediated carboxylation of benzylic C–H bonds with CO2 into 2-arylpropionic acids under metal-free conditions. Photo-oxidized triisopropylsilanethiol was used as the hydrogen atom transfer catalyst to afford a benzylic radical that accepts an electron from the reduced form of 2,3,4,6-tetra(9H-carbazol-9-yl)-5-(1-phenylethyl)benzonitrile generated in situ. The resulting benzylic carbanion reacts with CO2 to generate the corresponding carboxylic acid after protonation. The reaction proceeded without the addition of any sacrificial electron donor, electron acceptor or stoichiometric additives. Moderate to good yields of the desired products were obtained in a broad substrate scope. Several drugs were successfully synthesized using the novel strategy.

Photocatalysed eosin Y mediated C(sp3)-H alkylation of amine substrates via direct HAT

A visible light promoted, photoredox catalysed, green one-pot approach for the alkylation of amine substrates with sp2 carbon has been developed. This eosin Y based organic transformations, can behave as an effective direct hydrogen-atom transfer catalyst for coupling reaction. The proposed strategy includes simple procedure which can make adduct product with sp2 carbon. This eosin Y based photocatalytic hydrogen-atom transfer strategy may hold great potential for diverse functionalization of a wide range of native CH bonds in an economical and sustainable manner.

Regioselective intramolecular Markovnikov and anti-Markovnikov hydrofunctionalization of alkenes via photoredox catalysis.

Highly regioselective Markovnikov hydrofunctionalization of alkenes was successfully realized via photoredox catalysis by introducing a urea group and fine tuning the hydrogen atom transfer catalysts. The anti-Markovnikov hydroamination of alkenes was also achieved with high yields and stereoselectivities in this work.

Visible-light-mediated deuteration of silanes with deuterium oxide.

Isotopically labeled compounds are highly desirable as they can serve as both mechanistic probes in chemistry and diagnostic tools in medicinal research. Herein, we report an unprecedented visible-light-mediated metal-free deuteration of silanes using D2O as an inexpensive, readily available, and easy to handle deuterium source. A broad range of aryl- and alkyl-substituted silanes were deuterated with high deuterium incorporations and yields. Furthermore, a 100 gram-scale synthesis was demonstrated using continuous-flow micro-tubing reactors, where enhanced reaction efficiency was obtained. The photoredox-catalyzed polarity matched hydrogen atom transfer (HAT) between silanes and the thiol HAT catalyst was responsible for the efficient deuteration.

New Roles for Photoexcited Eosin Y in Photochemical Reactions.

Neutral eosin Y-derived photoexcited states have been found to serve as photoacids and direct hydrogen atom transfer (HAT) catalysts in the activation of glycals and C-H bonds, respectively. These studies pave the way for further use of eosin Y in photochemical synthesis.

Synergistic CO2 Mediation and Photocatalysis for α-Alkylation of Primary Aliphatic Amines

Recent work published by Rovis, Schoenebeck, and co-workers in Nature Chemistry describes a synergistic CO2 mediation and photocatalysis strategy for challenging α-alkylation of primary aliphatic amines by using quinuclidine as a hydrogen atom transfer (HAT) catalyst for γ-lactam synthesis. Electrostatic attraction between the in-situ-generated carbamate and quinuclidinium radical cation is critical for the selectivity.

Photocatalysis activates tough alkanes

Reactions that replace carbon-hydrogen bonds with other chemical moieties, called C–H activation reactions, have multiplied in recent years, seemingly spreading to every corner of chemical space. Yet a general method for the activation of light hydrocarbons has hovered just out of chemists’ reach. Because gaseous molecules like methane and ethane are insoluble in most solvents and contain notoriously inert C–H bonds, researchers have resorted to high pressures and temperatures to get the compounds to react with transition-metal catalysts. Now, an approach developed in Zhiwei Zuo’s lab at ShanghaiTech University leverages photocatalysis to promote the C–H functionalization of light alkanes under ambient conditions, except for methane, which required somewhat elevated pressures (Science 2018, DOI: 10.1126/science.aat9750). Using a cheap cerium catalyst and an alcohol hydrogen atom transfer catalyst lit by blue light-emitting diodes, the researchers performed C–H aminations, alkylations, and arylations of li...

Cooperative Catalysis: A Strategy To Synthesize Trifluoromethyl-thioesters from Aldehydes

A cooperative catalysis between a photoredox and a hydrogen atom transfer (HAT) catalyst has been developed to synthesize trifluoromethylthioesters from aldehydes. This reaction is mild, highly selective, operationally simple, works under redox neutral condition, and exhibits a broad substrate scope with high functional group tolerance. The synthetic utility of this method is demonstrated by the late-stage functionalization of bioactive molecules, making it amenable for drug discovery.