Direct enantioselective reduction of C=C bond ofβ-polyfluoro-alkylated enones via asymmetric photoredox catalysis

Direct enantioselective reduction of the C=C bond ofβ-polyfluoro-alkylated enones is an important but long-pending subject in asymmetric catalysis.Here,we report on the viability of visible light-driven cooperative photoredox and chiral hydrogenbonding catalysis to effectively address this challenge,as a variety of products are obtained in high yields(up to 85%)with good to excellent enantioselectivities(up to 98%ee).The formation of thermodynamically favorable enol intermediates after double single-electron reduction represents the center of the success.Additionally,the utility of the current method is validated by the convenient regio-specific and-diverse synthesis of various deuterated derivatives for these products using inexpensive D_(2)O as the deuterium source.

Modular synthesis of 1,4-diketones through regioselective bis-acylation of olefins by merging NHC and photoredox catalysis

Efficient and modular synthesis of structurally diverse 1,4-diketones from readily available building blocks represents an essential but challenging task in organic chemistry.Herein,we report a multi-component,regioselective bis-acylation of olefins by merging NHC organocatalysis and photoredox catalysis.With this protocol,a broad range of 1,4-diketones could be rapidly assembled using bench-stable feedstock materials.The robustness of this method was further evaluated by sensitivity screening,and good reproductivity was observed.Moreover,the diketone products could be readily converted into functionalized heterocycles,such as multi-substituted furan,pyrrole,and pyridazine.Mechanistic investigations shed light on the NHC and photoredox dual catalytic radical reaction mechanism.

Chlorine Atom Transfer of Unactivated Alkyl Chlorides Enabled by Zirconocene and Photoredox Catalysis

Alkyl chlorides are robust precursors to carbon radicals;however,their relative inertness has hampered their practical use.Although modern photochemical strategies have greatly enhanced the utility of alkyl chlorides as radical precursors,these methods often depend on strongly reducing conditions leading to unproductive side reactions.Here,we report a catalytic radical generation from 1°,2°,and 3°unactivated alkyl chlorides with zirconocene and photoredox catalysis,which enables both hydrogenation and borylation on a range of structurally complex molecules.This mild zirconocene-catalyzed protocol shows that zirconium can render the C−Cl bond cleavage more exergonic and can lower the activation energy of the transition state,amplifying the ability of metallocenes toward halogen atom transfer.

Valorization of Biomass-Derived Platform Molecules via Photoredox Sustainable Catalysis

The conversion of biomass into valuable chemicals has promise for application in biorefineries.Light-driven photoredox catalysis,with the typical features of green route and operation under mild conditions,is considered a promising strategy for renewable biomass or biomass-derived intermediates conversion into high-value-added chemical feedstocks.In this review,we strongly emphasize the recent advances in photocatalytic valorization of lignin model compounds and biomassderived alcohols.We briefl y summarize the advances in photocatalytic cleavage of theβ-O-4 bond or C–C bond into usable chemicals in the lignin model.On the other hand,we clarify not only the hybrid system for cooperative biomass-relevant alcohols oxidation and hydrogen(H2)evolution but also the tunable accessibility to variation of the target products from the same alcohol reactant by catalyst design and optimization of reaction conditions.It is hoped that this review will inspire the rational design of photoredox catalysis-based systems toward efficient biomass-derived platform molecules valorization to obtain target-oriented valuable products.

A review of enantioselective dual transition metal/photoredox catalysis

Transition metal catalysis is one of the most important tools to construct carbon-carbon and carbon-heteroatom bonds in modern organic synthesis. Visible-light photoredox catalysis has recently drawn considerable attention of the scientific community owing to its unique activation modes and significance for the green synthesis. The merger of photoredox catalysis with transition metal catalysts, termed metallaphotoredox catalysis, has become a popular strategy for expanding the synthetic utility of visiblelight photocatalysis. This strategy has led to the discovery of novel asymmetric transformations, which are unfeasible or not easily accessible by a single catalytic system. This contemporary area of organic chemistry holds promise for the development of economical and environmentally friendly methods for the asymmetric synthesis of chiral compounds. In this review, the advances in the enantioselective metallaphotoredox catalysis(EMPC) are summarized.

Photoredox Catalysis Unlocks the Nickel-Catalyzed Cyanation of Aryl Halides under Benign Conditions

The transition-metal-catalyzed cyanations of aryl halides are among the most used methods for synthesizing aryl nitriles.Despite tremendous advances,cyanating an aryl halide in a facile and benign fashion has generally been unsuccessful.The challenge in this significant transformation is the strong affinity of cyanide for metals,which hampers oxidative addition(OD)and reductive elimination(RE)making organometallic catalysis elusive.Herein,we demonstrate for the first time that photoredox-nickel-catalyzed cyanations of aryl halides are readily enabled by visible light,in which Ni(Ⅱ)species are transiently oxidized to Ni(Ⅲ)species,thereby facilitating subsequent cyanide transfer and RE.Using this dual catalysis strategy,we cyanated aryl and alkenyl halides at room temperature in a highly benign manner(30 examples,53-93% yield)by avoiding the use of air-sensitive ligands,Ni(0)precursors,and hypertoxic cyanation reagents,while also limiting excess metal waste.Computational studies were also used to help understand the present transformation.

Chemistry With N-Centered Radicals Generated by Single-Electron Transfer-Oxidation Using Photoredox Catalysis

This review covers the recent literature on oxidative generation of N-centered radicals using photoredox catalysis.The concept of proton-coupled electron transfer is briefly discussed.Applications of such reactive N-centered radicals in cascade processes comprising arene amidation,alkene amidation,C—C bond cleavage reactions,and remote C—H functionalization are addressed.In addition,novel reagents allowing for clean oxidative N-radical generation are discussed.

Benign perfluoroalkylation of uracils and uracil nucleosides via visible light-induced photoredox catalysis

In this work, an efficient and facile method for the preparation of 5-perfluoroalkylation uracils and uracil nucleosides through visible-light-mediated reaction has been developed. The reaction processes in high efficiency under mild reaction conditions and show broad substrate scope by employing commercial available perfluoroalkyl sources, thus demonstrates high potent application in life and medicinal science.

Alternating current electrolysis:A photoredox catalysis mimic and beyond

Alternating current electrolysis(ACE)is an emerging powerful synthetic tool,which principally resembles photoredox catalysis strategies.Its periodically alternating polarity feature allows oxidation and reduction processes to take place on the same electrode surface in a well-controlled manner via the fine-tuning of current frequency along with other reaction parameters.Therefore,many challenging transformations in typical direct electrolysis,including constant current electrolysis or constant potential electrolysis,could be achieved via ACE.The recent advances in the organic synthesis using this emerging technology and its advantages over direct electrolysis are highlighted.

Metallaphotoredox-Catalyzed Three-Component Couplings for Practical Synthesis of Ureas and Carbamates

Ureas are widely used in drugs,materials and catalysts because of their diamide structure,which can form strong hydrogen bonds.Therefore,it is of great scientific significance to develop efficient and green methods for the synthesis of urea compounds,especially unsymmetrical ureas.Here,we have disclosed novel and highly efficient three-component coupling reactions of organic halides,sodium cyanate and amines enabled by nickel/photoredox dual catalysis for the preparation of unsymmetrical ureas.The reaction features simple and safe operations,broad substrate scopes,and product diversities.It allows the facile synthesis of N-aryl/vinyl ureas from readily available,user-friendly feedstocks under mild conditions(27 examples,36%—98%yields).In addition,this method is further derived to alcohols as nucleophiles to synthesize a series of carbamates(15 examples,40%—95%yields).The mechanism experiment shows that the isocyanate produced by the coupling of halide and sodium cyanate may be the key intermediate in this reaction.

Photoredox catalytic alkylarylation of alkynes with arylsulfonylacetate as bifunctional reagent

Difunctionalization of alkynes represents a powerful and straightforward approach to the synthesis of complex molecules.However,the radical difunctionalization of alkynes mediated by bifunctional reagents remains challenging and underexplored,despite significant progress having been made in alkene difunctionalization.Here,we report a novel arylsulfonylacetate skeleton in which aryl rings are attached to acetates through SO_(2),serving as a powerful bifunctional reagent for the alkylarylation of alkynes via vinyl-radical intermediate under photoredox conditions.This modular bifunctional reagent enables the simultaneous incorporation of a wide range of functional groups,including(hetero)aryl ring and alkyl carboxylate into alkynes,resulting in synthetically valuable all-carbon tetrasubstituted alkene derivatives.This transformation is distinguished by its redox-neutral nature,readily accessible starting materials,compatibility with diverse functional groups and its capacity to facilitate convergent synthesis.The utility of this approach was further demonstrated by the late-stage functionalization of complex molecules and the preparation of fluorescent molecules and anti-cancer drugs.

Photoredox Synthesis of Thio-Functionalized Cyclic Ethers Using N-Sulfenyl Phthalimides as a Thiyl-Radical Precursor

Comprehensive Summary A visible-light mediated exclusively regioselective synthesis of 2,2-disubstituted thio-functionalized tetrahydrofurans,tetrahydro-pyrans and oxepanes has been described through an operationally simple and mild photoredox protocol.Thiyl radical generated from N-phenylsulfenyl phthalimide by photoredox catalysis was proven to be the key reactive intermediate in this reaction.

Metal-Free Photocatalytic[4+2]Annulation of Acrylamides with 2-Benzyl-2-bromocarbonyls to Assemble Tetralin-1-carboxamides

Tetralin-1-carboxamides are frequently incorporated in myriad medicinally important molecules.However,their existing synthetic routes not only suffer from some drawbacks such as tedious procedures,harsh reaction conditions,narrow substrate scope,low yields,and environmental problems,but are also based upon the elaboration of uneasily available non-linear tetralin derivatives.Herein,we describe a metal-and additive-free visible light-induced[4+2]annulation of two simple linear starting materials,namely acrylamides and 2-benzyl-2-bromocarbonyls,through a cascade C(sp^(3))-Br/C(sp^(2))-H bond cleavage,double C-C bond formation,and aromatization sequence.The developed protocol provides a convenient,efficient,and green approach to a variety of tetralin-1-carboxamide derivatives with good functional group compatibility.Importantly,the resulting products could also undergo the Licl-mediated mono-decarboxylative cyclization process to further furnish the architecturally novel bridged polycyclic imides with excellentcis-diastereoselectivities.

Recent advances in visible-light photoredox-catalyzed nitrogen radical cyclization

Visible-light photoredox catalysis is a powerful and attractive strategy for organic molecule activation and new reaction design owing to its environmental-friendly characteristics and unique catalytic mechanisms,and has found wide applications in organic synthesis.This catalytic strategy enables controllable generation of diverse nitrogen-centered radicals(NCRs)under mild conditions,providing access to construction of diverse nitrogencontaining compounds.In this review,we critically illustrate the recent advances in the field of visible-light photoredox-catalyzed cyclization of nitrogen-centered radicals,based on the different radical precursors and activation modes.Wherever possible,particular emphasis is also put on working models and synthetic applications.

Photoredox/palladium-cocatalyzed enantioselective alkylation of secondary benzyl carbonates with 4-alkyl-1,4-dihydropyridines

A photoredox/palladium-cocatalyzed enantioselective alkylation of racemic secondary carbonates with 4-alkyl-1,4-dihydropyridines under visible light irradiation has been developed. The present study provides a method for the preparation of optically active diarylalkanes from racemic diarylmethyl carbonates by a dynamic kinetic asymmetric transformation(DYKAT).This photoredox/palladium dual catalysis strategy expands the scope of the asymmetric Pd-catalyzed benzylic substitution reaction and serves as its potential alternative and complement.

Visible-light-induced photoredox-catalyzed synthesis of benzimidazo[2,1-a]iso-quinoline-6(5H)-ones

A simple and efficient visible-light-induced photo redox-catalyzed diarylation of N-methacryloyl-2-arylbenzoimidazoles with aryl diazonium salts was developed.The reaction provides a conve nient access to a variety of benzimidazoisoquinolinones through the construction of two C-C bonds in one step under mild reaction conditions.

Synthesis of Quaternary Carbon-Centered Benzoindolizidinones via Novel Photoredox-Catalyzed Alkene Aminoarylation: Facile Access to Tylophorine and Analogues

Photoredox-catalyzed aminoarylation and thioami-nation of unactivated alkenes have been developed,providing novel synthetic routes to access synthe-tically challenging quaternary carbon-centered benzoindolizidinones and trifluoromethylthiolated piperidines using readily available starting materials.Notably,these transformations were enabled by merging amidyl radical generation from N-alkyl benzamides with oxidant incorporation.Density functional theory calculations were performed to understand the reaction mechanism and to rationa-lize the regioselectivities.Moreover,the newly deve-loped catalytic aminoarylation provided a convenient synthetic route for natural product tylophorine and its gem-dimethyl analogues with greatly improved drug-like properties such as enhanced solubility and stability.

Photoredox-Catalyzed Hydrocarboxymethylation of Alkenes

Direct introduction of a carboxyl group into molecules is one of the most useful methods for the preparation of carboxylic acids,which avoids the conversion of various preexisting functional groups and features good step-and atom-economy.However,the methods for the direct synthesis of two-carbon added carboxylic acids from the precursors remain rare.Herein,we first report a general and mild method for the direct synthesis of a range of aliphatic acids by photoredox-catalyzed hydrocarboxymethylation of alkenes with good toleration of various functional groups in which bromoacetic acid is utilized as an ideal two-carbon synthon.

Photoredox Ni-Catalyzed Selective Coupling of Organic Halides and Oxalates to Esters via Alkoxycarbonyl Radical Intermediates

A new approach for radical cross coupling of organic halides and oxalates toward esters has been developed via photoredox nickel dual catalysis.This method has been demonstrated for transformation of a wide range of aryl,heteroaryl,alkenyl,and alkyl bromides to various esters under mild conditions.Notably,fluoro-,chloro-,or iodo-substituents on the aryl bromides remain after the coupling reaction,which has been applied for the easy synthesis of drug molecules from simple aryl dihalides.Mechanistic studies indicate that an(alkoxycarbonyl)Ni(I)species might be generated via oxidation of Ni(0)species with an alkoxycarbonyl radical intermediate.Selective alkoxycarbonyl radical coupling over decarboxylative alkyl radical coupling is achieved here.

Radical Mechanism of IrⅢ/NiⅡ Metallaphotoredox-Catalyzed C(sp^(3))-H Functionalization Triggered by Proton-Coupled Electron Transfer:Theoretical Insight

Photoredox catalysis can be induced to activate organic substrates or to modulate the oxidation state of transition-metal catalysts via unique singleelectron transfer processes,so as to achieve challenging C(sp^(3))-H functionalization under mild conditions.However,the specific reaction mechanism and relevant electron transfer process still need to be clarified.Here,a highly regioselective Ir^(Ⅲ)/Ni^(Ⅱ)-metallaphotoredox-catalyzed hydroalkylation of asymmetrical internal alkyne with an etherα-hetero C(sp^(3))-H bond has been investigated by density functional theory(DFT)calculations.A novel radical mechanism was predicted to merge oxidative quenching(Ir^(Ⅲ)-*Ir^(Ⅲ)-Ir^(Ⅳ)-Ir^(Ⅲ))and nickel catalytic cycles(NiⅡ-NiⅢ-NiI-NiⅢ-NiⅡ)for this C(sp^(3))-H functionalization to construct C(sp^(3))-C(sp^(2))bonds.It consists of seven major steps:the single-electron transfer involved in the photoredox cycle for generating active Ni(Ⅰ)-chloride complexes,proton-coupled electron transfer process to provide α-carbon-centered tetrahydrofuran(THF)radicals,radical capture by Ni(Ⅱ),reductive elimination to obtain 2-chlorotetrahydrofuran,alkyne oxidative hydrometallation,innersphere electron transfer,and σ-bond metathesis to yield the desired alkyne hydroalkylation product.Importantly,both the thermodynamic performance for redox potentials and the kinetic exploration for energy barriers and electron-transfer rates have also been evaluated for the corresponding electron transfer processes.In addition,the steric effects play a major role in determining the regioselectivity of alkyne oxidative hydrometallation.