Photoredox Catalysis Research Articles

Recent Discovery, Development, and Synthetic Applications of Formic Acid Salts in Photochemistry

AbstractThe advancement of sustainable photoredox catalysis in synthetic organic chemistry has evolved immensely because of the development of versatile and cost‐effective reagents. In recent years, a substantial effort has been dedicated to exploring the utility of formic acid salts in various photochemical reactions. In this context, formates have demonstrated diverse capabilities, functioning as reductants, sources of carbonyl groups, and reagents for hydrogen atom transfer. Notably, the CO2⋅– radical anion derived from formate exhibits strong reductant properties for cleaving both C−X and C−O bonds. Moreover, these salts play a pivotal role in carboxylation reactions, further highlighting their significance in a variety of photochemical transformations. The ability of formates to serve as reductants, carbonyl sources, and hydrogen atom transfer reagents reveal exciting possibilities in synthetic organic chemistry. This minireview highlights an array of captivating discoveries, underscoring the crucial role of formates in diverse and distinctive photochemical methods, enabling access to a wide range of value‐added compounds.

Recent Discovery, Development, and Synthetic Applications of Formic Acid Salts in Photochemistry.

The advancement of sustainable photoredox catalysis in synthetic organic chemistry has evolved immensely because of the development of versatile and cost-effective reagents. In recent years, a substantial effort has been dedicated to exploring the utility of formic acid salts in various photochemical reactions. In this context, formates have demonstrated diverse capabilities, functioning as reductants, sources of carbonyl groups, and reagents for hydrogen atom transfer. Notably, the CO2 ⋅- radical anion derived from formate exhibits strong reductant properties for cleaving both C-X and C-O bonds. Moreover, these salts play a pivotal role in carboxylation reactions, further highlighting their significance in a variety of photochemical transformations. The ability of formates to serve as reductants, carbonyl sources, and hydrogen atom transfer reagents reveal exciting possibilities in synthetic organic chemistry. This minireview highlights an array of captivating discoveries, underscoring the crucial role of formates in diverse and distinctive photochemical methods, enabling access to a wide range of value-added compounds.

Red-Light-Driven Atom Transfer Radical Polymerization for High-Throughput Polymer Synthesis in Open Air.

Photoinduced reversible-deactivation radical polymerization (photo-RDRP) techniques offer exceptional control over polymerization, providing access to well-defined polymers and hybrid materials with complex architectures. However, most photo-RDRP methods rely on UV/visible light or photoredox catalysts (PCs), which require complex multistep synthesis. Herein, we present the first example of fully oxygen-tolerant red/NIR-light-mediated photoinduced atom transfer radical polymerization (photo-ATRP) in a high-throughput manner under biologically relevant conditions. The method uses commercially available methylene blue (MB+) as the PC and [X-CuII/TPMA]+ (TPMA = tris(2-pyridylmethyl)amine) complex as the deactivator. The mechanistic study revealed that MB+ undergoes a reductive quenching cycle in the presence of the TPMA ligand used in excess. The formed semireduced MB (MB•) sustains polymerization by regenerating the [CuI/TPMA]+ activator and together with [X-CuII/TPMA]+ provides control over the polymerization. This dual catalytic system exhibited excellent oxygen tolerance, enabling polymerizations with high monomer conversions (>90%) in less than 60 min at low volumes (50-250 μL) and high-throughput synthesis of a library of well-defined polymers and DNA-polymer bioconjugates with narrow molecular weight distributions (Đ < 1.30) in an open-air 96-well plate. In addition, the broad absorption spectrum of MB+ allowed ATRP to be triggered under UV to NIR irradiation (395-730 nm). This opens avenues for the integration of orthogonal photoinduced reactions. Finally, the MB+/Cu catalysis showed good biocompatibility during polymerization in the presence of cells, which expands the potential applications of this method.

Highly Effective Near‐Infrared Light‐Activatable Triplet Fusion Upconversion with BODIPY Annihilators: Triplet Modulation via Non‐Conjugated n–π Spatial Electron Coupling

AbstractEffective strategies to manage the triplet state of chromophores are desirable in terms of their crucial role in photonic and optoelectronic technologies. However, triplet excited‐state energy level regulation of organic molecules remains elusive. Here, non‐conjugated n–π spatial electron coupling is demonstrated within boron‐dipyrromethene (BODIPY) and can greatly reduce the low‐lying triplet state (T1) to 1.34 eV without the conventional need for π‐conjugation extension. Moreover, the close alignment between T1 states of this BODIPY derivative and the photosensitizer PtTNP contributes to the reversible triplet energy transfer, namely the intermolecular triplet excited‐state equilibrium. Furthermore, to the best of the knowledge, the first BODIPY‐based near‐infrared light‐activated triplet fusion upconversion (NIR TF‐UC) with an upconversion quantum efficiency of 13.3% is implemented. On this basis, the air‐stable solid‐state NIR TF‐UC material is successfully fabricated, whose upconverted emission can still be seen at an ultralow NIR power density of 6.4 mW cm−2. This new strategy to implement triplet state modulation will accelerate the development of NIR TF‐UC and other important areas involving triplet state, such as photoredox catalysis, photodynamic therapy, and photovoltaic devices.

UVA‐Light‐Promoted Catalyst‐Free Photochemical Aerobic Oxidation of Boronic Acids

AbstractThe hydroxy group, and the phenol moiety in particular, is ubiquitous in several natural products, in organic synthesis and/or pharmaceutical industry. With the uprise of photoredox catalysis, many efforts worldwide focus on developing novel and sustainable protocols, providing an easy access to hydroxy‐containing molecules. Boronic acids and boronic ester derivatives are considered valuable precursors for the synthesis of hydroxy group derivatives. Herein, we report a novel, sustainable, light‐driven protocol, where the impact of wavelength irradiation on boronic acid aerobic photooxidation was examined. In this work, UVA‐light (370 nm) irradiation was found to promote the photocatalyst‐free aerobic oxidation of boronic acids and boronic acid derivatives. Furthermore, a broad scope of substrates was tested, and extensive mechanistic studies were performed in order to probe the reaction mechanism.

Unified Approach to Diverse Heterocyclic Synthesis: Organo-Photocatalyzed Carboacylation of Alkenes and Alkynes from Feedstock Aldehydes and Alcohols.

We report an organo-photocatalyzed carboacylation reaction that offers a springboard to create chemical complexity in a diversity-driven approach. The modular one-pot method uses feedstock aldehydes and alcohols as acyl surrogates and commercially available Eosin Y as the photoredox catalyst, making it simple and affordable to introduce structural diversity. Several biologically relevant skeletons have been easily synthesized under mild conditions in the presence of visible light irradiation by fostering a radical acylation/cyclization cascade. The proposed reaction mechanism was further illuminated by a number of spectroscopic studies. Furthermore, we applied this protocol for the late-stage functionalization of pharmaceuticals and blockbuster drugs.

Azoxy Compounds—From Synthesis to Reagents for Azoxy Group Transfer Reactions

AbstractThe azoxy functional group is an important structural motif and represents the formally oxidized counterpart of the azo group. Azoxy compounds find numerous applications ranging from pharmaceuticals to functional materials, yet their synthesis remains underdeveloped with a main focus on the formation symmetric azoxy compounds. To overcome challenges in the synthesis of such unsymmetric azoxy compounds, we designed a process employing readily accessible nitroso compounds and iminoiodinanes. This method builds on the use of visible light irradiation to generate a triplet nitrene from iminoiodinanes, which is trapped by nitroso arenes to give access to sulfonyl‐protected azoxy compounds with a good substrate scope and functional group tolerance. We further describe two applications of these sulfonyl‐protected azoxy compounds as radical precursors in synthesis, where the whole azoxy group can be transferred and employed in C(sp3)−H functionalization of ethers or 1,2‐difunctionalization of vinyl ethers. All of the reactions occurred at room temperature under visible light irradiation without the addition of any photoredox catalysts and additives. Control experiments, mechanism investigations, and DFT studies well explained the observed reactivity.

Azoxy Compounds-From Synthesis to Reagents for Azoxy Group Transfer Reactions.

The azoxy functional group is an important structural motif and represents the formally oxidized counterpart of the azo group. Azoxy compounds find numerous applications ranging from pharmaceuticals to functional materials, yet their synthesis remains underdeveloped with a main focus on the formation symmetric azoxy compounds. To overcome challenges in the synthesis of such unsymmetric azoxy compounds, we designed a process employing readily accessible nitroso compounds and iminoiodinanes. This method builds on the use of visible light irradiation to generate a triplet nitrene from iminoiodinanes, which is trapped by nitroso arenes to give access to sulfonyl-protected azoxy compounds with a good substrate scope and functional group tolerance. We further describe two applications of these sulfonyl-protected azoxy compounds as radical precursors in synthesis, where the whole azoxy group can be transferred and employed in C(sp3 )-H functionalization of ethers or 1,2-difunctionalization of vinyl ethers. All of the reactions occurred at room temperature under visible light irradiation without the addition of any photoredox catalysts and additives. Control experiments, mechanism investigations, and DFT studies well explained the observed reactivity.

Photocatalytic Hydrodecarboxylation of Fatty Acids for Drop-in Biofuels Production.

A mild, practical, and environmentally friendly method for the hydrodecarboxylation of fatty acids using an acridine-based photoredox catalyst and thiophenol was developed. Cn-1 alkanes were synthesized in good to excellent yields (up to 99 %) from C10-C18 saturated fatty acids under visible light irradiation (405 nm). The developed protocol was employed for a mixture of fatty acids obtained from the hydrolysis of Licuri oil, affording a mixture of C9-C17 hydrocarbons in quantitative yield, which demonstrates the potential application of the method to produce drop-in biofuels.

Photoinduced Copper-Catalyzed Enantioconvergent Remote Alkynylation via 1,4-Heteroaryl Migration.

A photoinduced copper-catalyzed enantioconvergent remote alkynylation of N-hydroxyphthalimide esters with terminal alkynes via 1,4-heteroaryl migration has been developed. A broad scope of heteroaryl-tethered chiral alkynes has been synthesized with good regio- and enantioselectivities. The chiral-ligand-coordinated copper species plays a dual role as both the photoredox and cross-coupling catalyst. This methodology provides a new platform for enantioconvergent remote alkynylations.

Impact of Alkyl Core Substitution Kinetics in Diaryl Dihydrophenazine Photoredox Catalysts on Properties and Performance in O-ATRP

Impact of Alkyl Core Substitution Kinetics in Diaryl Dihydrophenazine Photoredox Catalysts on Properties and Performance in O-ATRP

Asymmetric Cyanofunctionalization of Alkenes by Dual Copper and Photoredox Catalysis

Asymmetric Cyanofunctionalization of Alkenes by Dual Copper and Photoredox Catalysis

Synthesis of Sulfonamides Using Synergetic Photoredox and Copper Catalysis

Synthesis of Sulfonamides Using Synergetic Photoredox and Copper Catalysis

Exploiting the Marcus inverted region for first-row transition metal-based photoredox catalysis.

Second- and third-row transition metal complexes are widely employed in photocatalysis, whereas earth-abundant first-row transition metals have found only limited use because of the prohibitively fast decay of their excited states. We report an unforeseen reactivity mode for productive photocatalysis that uses cobalt polypyridyl complexes as photocatalysts by exploiting Marcus inverted region behavior that couples increases in excited-state energies with increased excited-state lifetimes. These cobalt (III) complexes can engage in bimolecular reactivity by virtue of their strong redox potentials and sufficiently long excited-state lifetimes, catalyzing oxidative C(sp2)-N coupling of aryl amides with challenging sterically hindered aryl boronic acids. More generally, the results imply that chromophores can be designed to increase excited-state lifetimes while simultaneously increasing excited-state energies, providing a pathway for the use of relatively abundant metals as photoredox catalysts.

Photo-catalyzedα-arylation of enol acetate using recyclable silica-supported heteroleptic and homoleptic copper(I) photosensitizers.

Earth-abundant photosensitizers are highly sought after for light-mediated applications, such as photoredox catalysis, depollution and energy conversion schemes. Homoleptic and heteroleptic copper(I) complexes are promising candidates in this field, as copper is abundant and the corresponding complexes are easily obtained in smooth conditions. However, some heteroleptic copper(I) complexes suffer from low (photo)stability that leads to the gradual formation of the corresponding homoleptic complex. Such degradation pathways are detrimental, especially when recyclability is desired. In here, we report a novel approach for the heterogenization of homoleptic and heteroleptic Cu complexes on silica nanoparticles. In both cases, the photophysical properties upon surface immobilization were only slightly affected. Excited-state quenching with aryl diazonium derivatives occurred efficiently (108-1010M-1s-1) with heterogeneous and homogeneous photosensitizers. Moderate but almost identical yields were obtained for thea-arylation of enol acetate using the homoleptic complex in homogeneous or heterogeneous conditions. Importantly, the silica-supported photocatalysts were recycled with moderate loss in photoactivity over multiple experiments. Transient absorption spectroscopy confirmed that excited-state electron transfer occurred from the homogeneous and heterogeneous homoleptic copper(I) complexes to aryl diazonium derivatives, generating the corresponding copper(II) center that persisted for several hundreds of microseconds, compatible with photoredox catalysis applications.

Photoredox-Catalyzed Phosphonocarboxylation of Allenes with Phosphine Oxides and CO2.

Phosphonocarboxylation of allenes with diarylphosphine oxides and CO2 via visible-light photoredox catalysis was developed for the first time. This work provided practical and sustainable access to highly valuable but otherwise difficult-to-access linear allylic β-phosphonyl carboxylic acids in moderate yields with exclusive regio- and stereoselectivity. This method was also characterized by step and atom economy and transition-metal free and mild conditions. Preliminary mechanistic studies suggested that allyl-methyl carbanion species are the key intermediates.

Visible-Light-Induced Oxidative Generation of o-Quinone Methides for Inverse-Electron-Demand [4+2] Cycloaddition Reactions

AbstractOrganophotoredox-catalyzed oxidative generation of o-quinone methides (o-QMs) for inverse-electron-demand [4+2] cycloaddition reactions has been developed. One-electron oxidation of 2-(sulfanylmethyl)phenols by thioxanthylium photoredox catalyst generated o-QMs, which reacted with various styrenes to produce chromanes with high regioselectivity. This reaction offers a valuable approach for in situ generating o-QMs via one-electron oxidation process under irradiation with mild green light.

Decarboxylative Nickel- and Photoredox-Catalyzed Aminocarbonylation of (Hetero)Aryl Bromides.

An efficient methodology for the photoredox- and nickel-catalyzed aminocarbonylation of (hetero)aryl bromides was developed. The utilization of readily available oxamic acids, the application of a broadly used organic photoredox catalyst (4CzIPN), and mild reaction conditions make this transformation an appealing alternative to classical amidation procedures. The generation of carbamoyl radicals was supported by trapping reactions with a hydrogen atom transfer catalyst in the presence of D2O, yielding the deuterated formamide. The generality of this deuteration protocol was confirmed for various oxamic acids.

Regioselective Hydrodeoxygenation of α-Diketones with Phosphites under Visible-Light Catalysis.

Novel regioselective hydrodeoxygenation of α-diketones with phosphites as the deoxygenation reagent was realized via visible-light photoredox catalysis. Broad substrate scope and high functional group compatibility were obtained. Unsymmetric α-diketones were selectively reduced at the carbonyls of higher electrophilicity. This unique regioselectivity compared with available methods makes it a practical complementary approach for the monohydrodeoxygenation of α-diketones.

A Paradigm Shift in Catalysis: Electro- and Photomediated Nickel-Catalyzed Cross-Coupling Reactions.

ConspectusTransition-metal catalyzed cross-coupling reactions are fundamental reactions in organic chemistry, facilitating strategic bond formations for accessing natural products, organic materials, agrochemicals, and pharmaceuticals. Redox chemistry enables access to elusive cross-coupling mechanisms through single-electron processes as an alternative to classical two-electron strategies predominated by palladium catalysis. The seminal reports of Baran, MacMillan, Doyle, Molander, Weix, Lin, Fu, Reisman, and others in merging redox perturbation (photochemical, electrochemical, and purely chemical) with catalysis are pivotal to the current resurgence and mechanistic understanding of first-row transition metal-based catalysis. The hallmark of this redox platform is the systematic modulation of transition-metal oxidation states by a photoredox catalyst or at a heterogeneous electrode surface. Electrocatalysis and photocatalysis enhance transition metal catalysis' capacity for bond formation through electron- or energy-transfer processes that promote otherwise challenging elementary steps or elusive mechanisms. Cross-coupling conditions promoted by electrocatalysis and photocatalysis are mild, and bond formation proceeds with exceptionally high chemoselectivity and wide functional group tolerance. The interfacing of abundant first-row transition-metal catalysis with electrocatalysis and photocatalysis has brought about a paradigm shift in cross-coupling technology as practitioners are quickly applying these tools in synthesizing fine chemicals and pharmaceutically relevant motifs. In particular, the merger of Ni catalysis with electro- and photochemistry ushered in a new era for carbon-carbon and carbon-heteroatom cross-couplings with expanded generality compared to their thermally driven counterparts. Over the past decade, we have developed enabling photo- and electrochemical methods throughout our combined research experience in industry (BMS, AstraZeneca) and academia (Professor Baran, Scripps Research) in cross-disciplinary collaborative environments. In this Account, we will outline recent progress from our past and present laboratories in photo- and electrochemically mediated Ni-catalyzed cross-couplings. By highlighting these cross-coupling methodologies, we will also compare mechanistic features of both electro- and photochemical strategies for forging C(sp2)-C(sp3), C(sp3)-C(sp3), C-O, C-N, and C-S bonds. Through these side-by-side comparisons, we hope to demystify the subtle differences between the two complementary tools to enact redox control over transition metal catalysis. Finally, building off the collective experience of ourselves and the rest of the community, we propose a tactical user guide to photo- and electrochemically driven cross-coupling reactions to aid the practitioner in rapidly applying such tools in their synthetic designs.