Photochemical C−H Hydroxyalkylation of Quinolines and Isoquinolines

We report herein a visible light‐mediated C?H hydroxyalkylation of quinolines and isoquinolines that proceeds via a radical path. The process exploits the excited‐state reactivity of 4‐acyl‐1,4‐dihydropyridines, which can readily generate acyl radicals upon blue light absorption. By avoiding the need for external oxidants, this radical‐generating strategy enables a departure from the classical, oxidative Minisci‐type pattern and unlocks a unique reactivity, leading to hydroxyalkylated heteroarenes. Mechanistic investigations provide evidence that a radical‐mediated spin‐center shift is the key step of the process. The method's mild reaction conditions and high functional group tolerance accounted for the late‐stage functionalization of active pharmaceutical ingredients and natural products.     

Visible‐Light‐Promoted Synthesis of 1,4‐Dicarbonyl Compounds via Conjugate Addition of Aroyl Chlorides

A facile visible‐light photocatalytic conjugate addition to prepare 1,4‐dicarbonyl compounds has been developed by employing readily available aroyl chlorides as aryl radical sources. This operationally simple method shows a broad scope with regard to both aroyl chlorides and Michael acceptors. As a result, a variety of 1,4‐diketones were efficiently synthesized in moderate to good yields.     

Organic Photocatalytic Cyclization of Polyenes: A Visible‐Light‐Mediated Radical Cascade Approach

A visible‐light‐mediated, organic photocatalytic stereoselective radical cascade cyclization of polyprenoids is described. The desired cascade cyclization products are achieved in good yields and high stereoselectivities with eosin Y as photocatalyst in hexafluoro‐2‐propanol. The catalyst system is also suitable for 1,3‐dicarbonyl compounds, which require only catalytic amounts of LiBr to promote the formation of the corresponding enols.     

Visible‐Light‐Promoted Cascade Radical Cyclization: Synthesis of 1,4‐Diketones Containing Chroman‐4‐One Skeletons

A visible‐light‐induced cascade radical cyclization of aroyl chlorides with 2‐(allyloxy)‐benzaldehyde derivatives has been developed. The method takes advantages of unactivated C=C bonds as the acyl radical acceptors and offers a mild and green approach for the synthesis of 1,4‐diketones bearing biologically important chroman‐4‐one skeletons with moderate to good yields.     

Visible‐Light‐Promoted Iminyl‐Radical Formation from Acyl Oximes: A Unified Approach to Pyridines,Quinolines, and Phenanthridines

A unified strategy involving visible‐light‐induced iminyl‐radical formation has been established for the construction of pyridines, quinolines, and phenanthridines from acyl oximes. With fac‐[Ir(ppy)₃] as a photoredox catalyst, the acyl oximes were converted by 1 e^? reduction into iminyl radical intermediates, which then underwent intramolecular homolytic aromatic substitution (HAS) to give the N‐containing arenes. These reactions proceeded with a broad range of substrates at room temperature in high yield. This strategy of visible‐light‐induced iminyl‐radical formation was successfully applied to a five‐step concise synthesis of benzo[c]phenanthridine alkaloids.     

Visible‐Light‐Promoted Iminyl‐Radical Formation from Acyl Oximes: A Unified Approach to Pyridines,Quinolines, and Phenanthridines

A unified strategy involving visible‐light‐induced iminyl‐radical formation has been established for the construction of pyridines, quinolines, and phenanthridines from acyl oximes. With fac‐[Ir(ppy)₃] as a photoredox catalyst, the acyl oximes were converted by 1 e⁻ reduction into iminyl radical intermediates, which then underwent intramolecular homolytic aromatic substitution (HAS) to give the N‐containing arenes. These reactions proceeded with a broad range of substrates at room temperature in high yield. This strategy of visible‐light‐induced iminyl‐radical formation was successfully applied to a five‐step concise synthesis of benzo[c]phenanthridine alkaloids.     

Exploration of a Chiral Cobalt Catalyst for Visible‐Light‐Induced Enantioselective Radical Conjugate Addition

Chiral catalysts tolerating photochemical reactions are in great demand for the vast development of visible‐light‐induced asymmetric synthesis. Now, chiral octahedral complexes based on earth‐abundant metal and chiral N₄ ligands are reported. One well‐defined chiral Co^II‐complex is shown to be an efficient catalyst in the visible‐light‐induced conjugated addition of enones by alkyl and acyl radicals, providing synthetically valued chiral ketones and 1,4‐dicarbonyls in 47–>99 % yields with up to 97:3 e.r.     

A Rhodium Catalyst Superior to Iridium Congeners for Enantioselective Radical Amination Activated by Visible Light

A bis‐cyclometalated rhodium(III) complex catalyzes a visible‐light‐activated enantioselective α‐amination of 2‐acyl imidazoles with up to 99 % yield and 98 % ee. The rhodium catalyst is ascribed a dual function as a chiral Lewis acid and, simultaneously, as a light‐activated smart initiator of a radical‐chain process through intermediate aminyl radicals. Notably, related iridium‐based photoredox catalysts reported before were unsuccessful in this enantioselective radical C?N bond formation. The surprising preference for rhodium over iridium is attributed to much faster ligand‐exchange kinetics of the rhodium complexes involved in the catalytic cycle, which is crucial to keep pace with the highly reactive and thus short‐lived nitrogen‐centered radical intermediate.     

Catalyst‐Dependent Chemoselective Formal Insertion of Diazo Compounds into C−C or C−H Bonds of 1,3‐Dicarbonyl Compounds

A catalyst‐dependent chemoselective one‐carbon insertion of diazo compounds into the C?C or C?H bonds of 1,3‐dicarbonyl species is reported. In the presence of silver(I) triflate, diazo insertion into the C(=O)?C bond of the 1,3‐dicarbonyl substrate leads to a 1,4‐dicarbonyl product containing an all‐carbon α‐quaternary center. This reaction constitutes the first example of an insertion of diazo‐derived carbenoids into acyclic C?C bonds. When instead scandium(III) triflate was applied as the catalyst, the reaction pathway switched to formal C?H insertion, affording 2‐alkylated 1,3‐dicarbonyl products. Different reaction pathways are proposed to account for this powerful catalyst‐dependent chemoselectivity.     

Light‐Driven Enantioselective Organocatalytic β‐Benzylation of Enals

A photochemical organocatalytic strategy for the direct enantioselective β‐benzylation of α,β‐unsaturated aldehydes is reported. The chemistry capitalizes upon the light‐triggered enolization of 2‐alkyl‐benzophenones to afford hydroxy‐o ‐quinodinomethanes. These fleeting intermediates are stereoselectively intercepted by chiral iminium ions, transiently formed upon condensation of a secondary amine catalyst with enals. Density functional theory (DFT) studies provided an explanation for why the reaction proceeds through an unconventional Michael‐type addition manifold, instead of a classical cycloaddition mechanism and subsequent ring‐opening.     

Metal‐Free C?H Bond Activation of Branched Aldehydes with a Hypervalent Iodine(III) Catalyst under Visible‐Light Photolysis: Successful Trapping with Electron‐Deficient Olefins

Direct acyl radical formation of linear aldehydes (RCH₂‐CHO) and subsequent hydroacylation with electron‐deficient olefins can be effected with various types of metal and nonmetal catalysts/reagents. In marked contrast, however, no successful reports on the use of branched aldehydes have been made thus far because of their strong tendency of generating alkyl radicals through the facile decarbonylation of acyl radicals. Here, use of a hypervalent iodine(III) catalyst under visible light photolysis allows a mild way of generating acyl radicals from various branched aldehydes, thereby giving the corresponding hydroacylated products almost exclusively. Another characteristic feature of this approach is the catalytic use of hypervalent iodine(III) reagent, which is a rare example on the generation of radicals in hypervalent iodine chemistry.     

Metal‐Free CH Bond Activation of Branched Aldehydes with a Hypervalent Iodine(III) Catalyst under Visible‐Light Photolysis: Successful Trapping with Electron‐Deficient Olefins

Direct acyl radical formation of linear aldehydes (RCH₂‐CHO) and subsequent hydroacylation with electron‐deficient olefins can be effected with various types of metal and nonmetal catalysts/reagents. In marked contrast, however, no successful reports on the use of branched aldehydes have been made thus far because of their strong tendency of generating alkyl radicals through the facile decarbonylation of acyl radicals. Here, use of a hypervalent iodine(III) catalyst under visible light photolysis allows a mild way of generating acyl radicals from various branched aldehydes, thereby giving the corresponding hydroacylated products almost exclusively. Another characteristic feature of this approach is the catalytic use of hypervalent iodine(III) reagent, which is a rare example on the generation of radicals in hypervalent iodine chemistry.     

Combination of transition metal carbonyls and silanes: New photoinitiating systems

The recently developed silyl radical chemistry is used in combination with transition metal carbonyls MC (dimanganese(0) decacarbonyl; dirhenium decacarbonyl; cyclopentadienyl iron(II) dicarbonyl dimer) for both free radical promoted cationic photopolymerization (FRPCP) and free radical photopolymerization (FRP). The newly developed photoinitiating systems (MC/silane and MC/silane/iodonium salt) are highly efficient under air. Photopolymerization profiles obtained upon a visible light irradiation delivered by a xenon lamp show that high conversion can be easily achieved after a 400 s exposure. Sunlight irradiations under air can also lead to tack free coatings. The processes associated with the metal carbonyl radical/silane interactions are investigated by Laser Flash Photolysis (LFP) and ESR‐Spin Trapping (ESR‐ST) experiments. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1830–1837, 2010     

Dual Hypervalent Iodine(III) Reagents and Photoredox Catalysis Enable Decarboxylative Ynonylation under Mild Conditions

A combination of hypervalent iodine(III) reagents (HIR) and photoredox catalysis with visible light has enabled chemoselective decarboxylative ynonylation to construct ynones, ynamides, and ynoates. This ynonylation occurs effectively under mild reaction conditions at room temperature and on substrates with various sensitive and reactive functional groups. The reaction represents the first HIR/photoredox dual catalysis to form acyl radicals from α‐ketoacids, followed by an unprecedented acyl radical addition to HIR‐bound alkynes. Its efficient construction of an mGlu5 receptor inhibitor under neutral aqueous conditions suggests future visible‐light‐induced biological applications.     

Visible‐Light Promoted Catalyst‐Free Imidation of Arenes and Heteroarenes

We described herein a catalyst‐free visible‐light photolytic protocol for the imidation of arenes and heteroarenes. N‐Bromosaccharin was identified as a viable and chemoselective nitrogen radical precursor that undergoes controllable homolytic cleavage under ambient light irradiation. The reaction can be applied to a number of arenes and heteroarenes with good chemo‐ and regioselectivity. Mechanistic studies revealed that radical chain termination by electron transfer‐proton transfer (ET‐PT) is the leading productive pathway for the reaction.     

Enantioselective Hydroamidation of Enals by Trapping of a Transient Acyl Species

An enantioselective synthesis of β‐chiral amides through asymmetric and redox‐neutral hydroamidation of enals is reported. In this reaction, a chiral N‐heterocyclic carbene (NHC) catalyst reacts with enals to generate the homoenolate intermediate. Upon highly enantioselective β‐protonation through proton‐shuttle catalysis, the resulting azolium intermediate reacts with imidazole to yield the key β‐chiral acyl species. This transient intermediate provides access to diversified β‐chiral carbonyl derivatives, such as amides, hydrazides, acids, esters, and thioesters. In particular, β‐chiral amides can be prepared in excellent yield and ee (40 chiral amides, up to 95 % yield and 99 % ee). This modular strategy overcomes the challenge of disruption of the highly selective proton‐shuttling process by basic amines.     

A Photochemical Organocatalytic Strategy for the α‐Alkylation of Ketones by using Radicals

Reported herein is a visible‐light‐mediated radical approach to the α‐alkylation of ketones. This method exploits the ability of a nucleophilic organocatalyst to generate radicals upon S_N2‐based activation of alkyl halides and blue light irradiation. The resulting open‐shell intermediates are then intercepted by weakly nucleophilic silyl enol ethers, which would be unable to directly attack the alkyl halides through a traditional two‐electron path. The mild reaction conditions allowed functionalization of the α position of ketones with functional groups that are not compatible with classical anionic strategies. In addition, the redox‐neutral nature of this process makes it compatible with a cinchona‐based primary amine catalyst, which was used to develop a rare example of enantioselective organocatalytic radical α‐alkylation of ketones.     

Visible light induced C-H monofluoroalkylation to synthesize 1,4-unsaturated compound

We developed a method to synthesize fluorinated 1,4-unsaturated dicarbonyl compounds via photoredox catalyzed radical addition process. Commercially available ethyl bromodifluoroacetate (BrCF₂CO₂Et) as fluoroalkyl source, the corresponding fluoro-containing dicarbonyl compounds could be obtained in moderate to good yields.     

Acyl Radicals from Aromatic Carboxylic Acids by Means of Visible‐Light Photoredox Catalysis

Simple and abundant carboxylic acids have been used as acyl radical precursor by means of visible‐light photoredox catalysis. By the transient generation of a reactive anhydride intermediate, this redox‐neutral approach offers a mild and rapid entry to high‐value heterocyclic compounds without the need of UV irradiation, high temperature, high CO pressure, tin reagents, or peroxides.     

A Visible‐Light‐Driven Iminyl Radical‐Mediated C−C Single Bond Cleavage/Radical Addition Cascade of Oxime Esters

A room‐temperature, visible‐light‐driven N‐centered iminyl radical‐mediated and redox‐neutral C?C single bond cleavage/radical addition cascade reaction of oxime esters and unsaturated systems has been accomplished. The strategy tolerates a wide range of O‐acyl oximes and unsaturated systems, such as alkenes, silyl enol ethers, alkynes, and isonitrile, enabling highly selective formation of various chemical bonds. This method thus provides an efficient approach to various diversely substituted cyano‐containing alkenes, ketones, carbocycles, and heterocycles.