Visible Light-mediated Photoredox Research Articles

Visible light mediated decarboxylative difluoroalkylations of cyclic N-sulfonyl ketimines: Efficient synthesis of difluoroalkylated Cα-tetrasubstituted α-amino acid derivatives

An efficient decarboxylative difluoroalkylation method of cyclic N-sulfonyl ketimines with difluoroalkyl carboxylates has been developed through visible light-mediated photoredox catalysis process. This protocol provides a straightforward route for the synthesis of difluoroalkylated Cα-tetrasubstituted α-amino acid derivatives in moderate to good yields with excellent functional group tolerance under mild and simple conditions.

Access to All-Carbon Quaternary Centers by Photocatalytic Fluoroalkylation of α-Halo Carbonyl Compounds.

Perfluoroalkyl groups have become significantly important in pharmaceutical and agrochemical applications. In this study, we present a visible light-mediated photoredox neutral strategy for the fluoroalkylation of tertiary alkyl chlorides under transition-metal-free conditions. This method allows for the facile synthesis of fluoroalkylated all-carbon quaternary centers, exhibiting excellent functional group compatibility. Mechanistic studies reveal the involvement of two reactive radical intermediates and the in situ formation of metal enolates in a radical-polar crossover manner. The versatility of this methodology is demonstrated through synthetic transformations based on the carbonyl group, showcasing its potential for the rapid assembly of diverse organic molecules bearing fluoroalkyl all-carbon quaternary centers.

Visible Light-Driven Metal-Organic Framework-Mediated Activation and Utilization of CO2 for the Thiocarboxylation of Olefins.

Visible light-mediated photoredox catalysis has emerged to be a fascinating approach for the activation of CO2 and its subsequent fixation into valuable chemicals utilizing renewable and inexhaustible solar energy. Although great progress has been made in CO2 photoreduction, visible light-assisted organic synthesis using CO2 as a reactive substrate is rarely explored. Herein, we report an efficient, facile, and economically viable photoredox-mediated approach for the synthesis of important β-thioacids via carboxylation of olefins with CO2 and thiols over a porous functionalized metal-organic framework (MOF), Fe-MIL-101-NH2, as a photocatalyst under ambient conditions. This multicomponent reaction offers wide substrate scope, mild reaction conditions, easy work-up, cost-effective and reusable photocatalysts, and higher product selectivity. Computational studies suggested that CO2 interacts with the thiophenol-styrene adduct to facilitate the synthesis of β-thioacids in almost quantitative yields.

NHC and visible light-mediated photoredox co-catalyzed 1,4-sulfonylacylation of 1,3-enynes for tetrasubstituted allenyl ketones.

The modulation of selectivity of highly reactive carbon radical cross-coupling for the construction of C–C bonds represents a challenging task in organic chemistry. N-Heterocyclic carbene (NHC) catalyzed radical transformations have opened a new avenue for acyl radical cross-coupling chemistry. With this method, highly selective cross-coupling of an acyl radical with an alkyl radical for efficient construction of C–C bonds was successfully realized. However, the cross-coupling reaction of acyl radicals with vinyl radicals has been much less investigated. We herein describe NHC and visible light-mediated photoredox co-catalyzed radical 1,4-sulfonylacylation of 1,3-enynes, providing structurally diversified valuable tetrasubstituted allenyl ketones. Mechanistic studies indicated that ketyl radicals are formed from aroyl fluorides via the oxidative quenching of the photocatalyst excited state, allenyl radicals are generated from chemo-specific sulfonyl radical addition to the 1,3-enynes, and finally, the key allenyl and ketyl radical cross-coupling provides tetrasubstituted allenyl ketones.

A Unified Strategy to Access 2- and 4-Deoxygenated Sugars Enabled by Manganese-Promoted 1,2-Radical Migration.

The selective manipulation of carbohydrate scaffolds is challenging due to the presence of multiple, nearly chemically indistinguishable O-H and C-H bonds. As a result, protecting-group-based synthetic strategies are typically necessary for carbohydrate modification. Here we report a concise semisynthetic strategy to access diverse 2- and 4-deoxygenated carbohydrates without relying on the exhaustive use of protecting groups to achieve site-selective reaction outcomes. Our approach leverages a Mn2+-promoted redox isomerization step, which proceeds via sugar radical intermediates accessed by neutral hydrogen atom abstraction under visible light-mediated photoredox conditions. The resulting deoxyketopyranosides feature chemically distinguishable functional groups and are readily transformed into diverse carbohydrate structures. To showcase the versatility of this method, we report expedient syntheses of the rare sugars l-ristosamine, l-olivose, l-mycarose, and l-digitoxose from commercial l-rhamnose. The findings presented here validate the potential for radical intermediates to facilitate the selective transformation of carbohydrates and showcase the step and efficiency advantages attendant to synthetic strategies that minimize a reliance upon protecting groups.

Controlling Radical Relay Processes with Visible Light

Harnessing free radical intermediates for selective functionalization of organic compounds has been widely demonstrated under photocatalytic conditions requiring a distinct photocatalyst. In this issue of Chem, Seo, Chang, and co-workers demonstrate an alternative photocatalyst-free light-mediated approach that allows efficient amidation of aldehydes via N-centered radical intermediate.

Highly chemoselective deoxygenation of N-heterocyclic N-oxides under transition metal-free conditions.

Because their site-selective C-H functionalizations are now considered one of the most useful tools for synthesizing various N-heterocyclic compounds, the highly chemoselective deoxygenation of densely functionalized N-heterocyclic N-oxides has received much attention from the synthetic chemistry community. Here, we provide a protocol for the highly chemoselective deoxygenation of various functionalized N-oxides under visible light-mediated photoredox conditions with Na2-eosin Y as an organophotocatalyst. Mechanistic studies imply that the excited state of the organophotocatalyst is reductively quenched by Hantzsch esters. This operationally simple technique tolerates a wide range of functional groups and allows high-yield, multigram-scale deoxygenation.

Visible light-mediated synthesis of amides from carboxylic acids and amine-boranes

A practical method for the amidation reaction between carboxylic acids and amines was developed, for the first time, through a visible light-mediated photoredox deoxygenation at room temperature.

Rapid Photocrosslinking of Silk Hydrogels with High Cell Density and Enhanced Shape Fidelity.

Silk fibroin hydrogels crosslinked through di-tyrosine bonds are clear, elastomeric constructs with immense potential in regenerative medicine applications. In this study, demonstrated is a new visible light-mediated photoredox system for di-tyrosine bond formation in silk fibroin that overcomes major limitations of current conventional enzymatic-based crosslinking. This photomediated system rapidly crosslinks silk fibroin (<1 min), allowing encapsulation of cells at significantly higher cell densities (15 million cells mL-1 ) while retaining high cell viability (>80%). The photocrosslinked silk hydrogels present more stable mechanical properties which do not undergo spontaneous transition to stiff, β-sheet-rich networks typically seen for enzymatically crosslinked systems. These hydrogels also support long-term culture of human articular chondrocytes, with excellent cartilage tissue formation. This system also facilitates the first demonstration of biofabrication of silk fibroin constructs in the absence of chemical modification of the protein structure or rheological additives. Cell-laden constructs with complex, ordered, graduated architectures, and high resolution (40 µm) are fabricated using the photocrosslinking system, which cannot be achieved using the enzymatic crosslinking system. Taken together, this work demonstrates the immense potential of a new crosslinking approach for fabrication of elastomeric silk hydrogels with applications in biofabrication and tissue regeneration.

Stereoselective Total Synthesis of Aspergillide A: A Visible Light-Mediated Photoredox Access to the Trisubstituted Tetrahydropyran Core.

A stereoselective total synthesis of natural product aspergillide A is reported. The adopted strategy relies on the direct access to the key tetrahydropyran core through a visible light-mediated photoredox reaction from an allylic alcohol and iodoacetic acid. In a single manipulation, a γ-iodo-δ-valerolactone is obtained through an atom transfer radical addition followed by in situ acid-catalyzed lactonization. The obtained lactone possesses three functionalized sites, which were seized to link the required substituents in the final product and thus completing the total synthesis of aspergillide A.

Synthesis and characterisation of homoleptic 2,9-diaryl-1,10-phenanthroline copper(i) complexes: influencing selectivity in photoredox-catalysed atom-transfer radical addition reactions.

This report details the synthesis and characterisation of eight homoleptic bis(2,9-diaryl-1,10-phenanthroline)copper(i) complexes, seven of which are previously unreported {aryl = p-CF3C6H4, p-FC6H4, m,p-(OMe)2C6H3, o,p-(OMe)2C6H3, p-OMe-m,m-Me2C6H2, p-OMe-m,m-(t-Bu)2C6H2, 9,9-dimethyl-9H-fluoren-2-yl, 4-(9H-carbazol-9-yl)phenyl)}. Where possible the solid state, photophysical and electrochemical properties of these complexes were studied. In order to obtain insights into the influence of the intrinsic features of these copper(i) complexes on their reactivity in visible light-mediated photoredox catalysis, their capacity to promote a known atom-transfer radical addition process was evaluated. This specific transformation was identified as a suitable model system as it is reported to proceed via a mechanism consistent with the inner-sphere reactivity enabled by coordinatively unsaturated phenanthroline-based copper(i) species.

Recent Applications of [Cu(dap)2]Cl in Visible Light-Mediated Photoredox Catalysis

Since 2008, visible light-mediated photoredox catalysis has enjoyed a renaissance in organic synthesis. [1–5] The most commonly employed metal-based photoredox catalysts typically utilise second- and third-row transition metals featuring polypyridyl ligand systems such as [Ru(bpy) 3 ]Cl 2 (1). [1] In contrast, the synthetic applications of copper-based photoredox catalysts have received much less attention. [6] A class of photoactive homoleptic, phenanthroline-based copper(I) complexes, including [Cu (dap) 2 ]Cl (2), were first prepared some 35 years ago (Chart 1). [7,8] This class of complexes share several interesting properties that can be exploited to facilitate chemical transformations. The absorption of a photon in the visible range leads to a metal-to-ligand charge transfer (MLCT) excited state. Subsequent intersystem crossing (ISC) results in spin inversion and allows access to long-lived triplet photoexcited states. [9] In its photoexcited state, complex 2 is a strong reductant (-1.43 V versus saturated calomel electrode) capable of reducing organic acceptor molecules via single electron transfer (SET) processes. [8] The ensuing CuIIspecies can undergo a second SET process to oxidise an organic donor molecule, which reduces the catalyst back to its ground state and closes the catalytic cycle. [1] The coordinatively unsaturated nature of these copper(I) complexes typically provides lower coordinative stability relative to saturated octahedral complexes (e.g. 1). Also, in the ground state, these copper(I) complexes typically exhibit a distorted tetrahedral coordination geometry. Upon photoexcitation, oxidation of the metal centre occurs as a result of the population of the MLCT excited state. This causes a flattening distortion that results in a more square-planar coordination geometry. These two factors are primarily responsible for reducing excited state lifetimes. The present focus article aims to highlight recent applications of [Cu(dap) 2 ]Cl in organic synthesis.

Visible light mediated reductions of ethers, amines and sulfides

Abstract Visible light-mediated photoredox catalysis enables the chemoselective reduction of activated carbon–heteroatom bonds as a function of reduction potential. The expansion of the scope of C–X bond reductions towards less activated motifs, such as ethers, amines and sulfides, is important to both organic synthesis and macromolecular degradation method development. In the present report, exploration of photoredox catalysis in alcoholic solvents mediated a decrease in the super-stoichiometric use of i Pr 2 NEt and HCO 2 H in the reduction of α-keto ethers, amines and sulfides. Additionally, in the absence of fragmentation, C C bond formation was afforded, suggesting an intermediate ketyl radicals are present in these transformations.

ORGANIC CHEMISTRY. Enchained by visible light-mediated photoredox catalysis.

Radical-chain processes can dominate the kinetics of photogenerated radical catalysis

Ligand functionalization as a deactivation pathway in a fac-Ir(ppy)3-mediated radical addition.

Knowledge of the kinetic behavior of catalysts under synthetically relevant conditions is vital for the efficient use of compounds that mediate important transformations regardless of their composition or driving force. In particular, these data are of great importance to add perspective to the growing number of applications of photoactive transition metal complexes. Here we present kinetic, synthetic, and spectroscopic evidence of the mechanistic behavior of fac-Ir(ppy)3 in a visible light-mediated radical addition to 3-methylindole, demonstrating the instability of fac-Ir(ppy)3 under these conditions. During the reaction, rapid in situ functionalization of the photocatalyst occurs, eventually leading to deactivation. These findings demonstrate a conceivable deactivation process for catalytic single electron reactions in the presence of radicophilic ligands. Attempts to inhibit photocatalyst deactivation through structural modification provide further insight into catalyst selection for a given system of interest.

ChemInform Abstract: Decarboxylative Arylation of α‐Amino Acids via Photoredox Catalysis: A One‐Step Conversion of Biomass to Drug Pharmacophore.

The direct decarboxylative arylation of α-amino acids has been achieved via visible light-mediated photoredox catalysis. This method offers rapid entry to prevalent benzylic amine architectures from an abundant biomass, specifically α-amino acid precursors. Significant substrate scope is observed with respect to both the amino acid and arene components.

Carboxylic acids as a traceless activation group for conjugate additions: a three-step synthesis of (±)-pregabalin.

The direct application of carboxylic acids as a traceless activation group for radical Michael additions has been accomplished via visible light-mediated photoredox catalysis. Photon-induced oxidation of a broad series of carboxylic acids, including hydrocarbon-substituted, α-oxy, and α-amino acids, provides a versatile CO2-extrusion platform to generate Michael donors without the requirement for organometallic activation or propagation. A diverse array of Michael acceptors is amenable to this new conjugate addition strategy. An application of this technology to a three-step synthesis of the medicinal agent pregabalin (commercialized by Pfizer under the trade name Lyrica) is also presented.

Decarboxylative Arylation of α-Amino Acids via Photoredox Catalysis: A One-Step Conversion of Biomass to Drug Pharmacophore

The direct decarboxylative arylation of α-amino acids has been achieved via visible light-mediated photoredox catalysis. This method offers rapid entry to prevalent benzylic amine architectures from an abundant biomass, specifically α-amino acid precursors. Significant substrate scope is observed with respect to both the amino acid and arene components.

Visible Light-mediated Direct Arylation of Arenes and Heteroarenes Using Diaryliodonium Salts in the Presence and Absence of a Photocatalyst

Abstract Diaryliodonium salts have been used as aryl radical sources under visible light-mediated photoredox catalysis. Benzene and a range of heteroarenes are arylated with Ar2I+ in the presence of [Ir(ppy)2(bpy)]PF6 upon irradiation with visible light. When pyrroles are used, the arylation proceeds in the absence of a photoredox catalyst. Both processes are initiated by photoinduced single-electron-transfer to Ar2I+, generating aryl radicals.

Synthesis of symmetric anhydrides using visible light-mediated photoredox catalysis

A new approach to anhydride formation is reported via activation of C-O bonds by the Vilsmeier-Haack reagent formed by Ru(bpy)(3)Cl(2) and CBr(4) in DMF. Various aryl and alkyl carboxylic acids are converted to the corresponding anhydrides in excellent yields.