Photoredox Catalysis Research Articles

Near-Infrared Absorbing Aza-BODIPY Dyes for Optoelectronic Applications.

Organic dyes that absorb light in the visible to near-infrared region have garnered significant interest, owing to their extensive utility in organic photovoltaics and various biomedical applications. Aza-boron-dipyrromethene (Aza-BODIPY) dyes are a class of chromophores with impressive photophysical properties such as tunable absorption from the visible region towards near infrared (NIR) region, high molar absorptivity, and fluorescence quantum yield. In this review, we discuss the developments in the aza-BODIPYs, related to their synthetic routes, photophysical properties and their applications. Their design strategies, modifications in chemical structures, mode/position of attachment, and their impact on photo-physical properties are reviewed. The potential applications of aza-BODIPY derivatives such as organic solar cells, photodynamic therapy, boron-neutron capture therapy, fluorescence sensors, photo-redox catalysis, photoacoustic probes and optoelectronic devices are explained.

Red-light-mediated copper-catalyzed photoredox catalysis promotes regioselectivity switch in the difunctionalization of alkenes

Controlling regioselectivity during difunctionalization of alkenes remains a significant challenge, particularly when the installation of both functional groups involves radical processes. In this aspect, methodologies to install trifluoromethane (−CF3) via difunctionalization have been explored, due to the importance of this moiety in the pharmaceutical sectors; however, these existing reports are limited, most of which affording only the corresponding β-trifluoromethylated products. The main reason for this limitation arises from the fact that −CF3 group served as an initiator in those reactions and predominantly preferred to be installed at the terminal (β) position of an alkene. On the contrary, functionalization of the −CF3 group at the internal (α) position of alkenes would provide valuable products, but a meticulous approach is necessary to win this regioselectivity switch. Intrigued by this challenge, we here develop an efficient and regioselective strategy where the −CF3 group is installed at the α-position of an alkene. Molecular complexity is achieved via the simultaneous insertion of a sulfonyl fragment (−SO2R) at the β-position. A precisely regulated sequence of radical generation using red light-mediated photocatalysis facilitates this regioselective switch from the terminal (β) position to the internal (α) position. Furthermore, this approach demonstrates broad substrate scope and industrial potential for the synthesis of pharmaceuticals under mild reaction conditions.

Sulfonamide-directed site-selective functionalization of unactivated C(sp3)−H enabled by photocatalytic sequential electron/proton transfer

The generation of alkyl radical from C(sp3)−H substrates via hydrogen atom abstraction represents a desirable yet underexplored strategy in alkylation reaction since involving common concerns remain adequately unaddressed, such as the harsh reaction conditions, limited substrate scope, and the employment of noble metal- or photo-catalysts and stoichiometric oxidants. Here, we utilize the synergistic strategy of photoredox and hydrogen atom transfer (HAT) catalysis to accomplish a general and practical functionalization of unactived C(sp3)−H centers with broad reaction scope, high functional group compatibility, and operational simplicity. A combination of validation experiments and density functional theory reveals that the N-centered radicals, generated from free N − H bond in a stepwise electron/proton transfer event, are the key intermediates that enable an intramolecular 1,5-HAT or intermolecular HAT process for nucleophilic carbon-centered radicals formation to achieve heteroarylation, alkylation, amination, cyanation, azidation, trifluoromethylthiolation, halogenation and deuteration. The practical value of this protocol is further demonstrated by the gram-scale synthesis and the late-stage functionalization of natural products and drug derivatives.

Carrier dynamics competition in the nanocrystal-molecule complex for triplet generation studied by transient-absorption spectroscopy

Owing to the long-lived decay of triplet excited state, extensive efforts have been devoted to efficient triplet generation for applications covering triplet–triplet annihilation for photon upconversion, photocycloaddition and photoredox catalysis. Among the candidates, nanocrystal-molecule complexes have received tremendous attention for triplet generation because of easier spin flip and negligible energy loss during intersystem crossing. However, the triplet energy transfer (TET) from nanocrystals (NCs) to molecules can be very complicated in actual situation due to intricate energy level alignment and inevitable defect states, which often involves various decay pathes of the excited state competing with TET. Understanding the detailed carrier dynamics in such complexes is strongly necessary for related applications. Here, a CdSe-TCA (5-tetracene carboxylic acid) complex with a Type-II like energy level alignment is synthesized through precisely adjusting the dimension of CdSe NC. Based on series of spectral measurements, especially the transient absorption (TA) spectroscopy, the results show various carrier dynamics including hole-transfer-mediated TET, Förster resonance energy transfer (FRET) and carrier trapping. Although the carrier trapping by defect states in CdSe NC is revealed not associated with the TET from CdSe to TCA, the FRET is proved to competing with the TET process. Both the FRET and defect states should be refrained for efficient TET in such complexes. This study could provide further insight for understanding the carrier dynamics competition in NC-molecule complexes for triplet generation and benefit related optoelectronics applications.

Thiobenzoic Acid-Catalyzed Cα-H Cross Coupling of Benzyl Alcohols with α-Ketoacid Derivatives.

The C-H alkylation of benzyl alcohols with α-ketoacid derivatives was achieved in the presence of thiobenzoic acid with or without Ru or Ir photoredox catalysts. The thiobenzoic acid serves as a photoexcited single-electron reducing reagent and a hydrogen atom transfer catalyst, while addition of the metal photoredox catalyst assists the electron transfer and improves the reaction efficiency. Various functional groups were tolerant of the reaction conditions, and sterically hindered diols were produced in good to high yield.

C-H Bond Sulfonylation from Thianthrenium Salts and DABCO·(SO2)2: Synthesis of 2-Sulfonylindoles.

A three-component reaction of 1-(1H-indol-1-yl)isoquinolines or 1-(pyridin-2-yl)-1H-indoles, DABCO·(SO2)2, and thianthrenium salts under synergistic photoredox and palladium catalysis is accomplished. This direct C-H bond sulfonylation of indoles with the insertion of sulfur dioxide under mild conditions works efficiently, giving rise to a wide range of 2-sulfonated indoles in moderate to good yields under mild conditions. In this protocol, the generality of aryl/alkyl thianthrenium salts is demonstrated as well. A photoredox radical process combined with palladium catalysis is proposed.

Merging Photoredox and Nickel Catalysis: A Ligand-Free Cross-Coupling of Vinyl Halides and α-Silylamines toward Tertiary Allylic Alkylamines

Merging Photoredox and Nickel Catalysis: A Ligand-Free Cross-Coupling of Vinyl Halides and α-Silylamines toward Tertiary Allylic Alkylamines

Sequential closed-loop Bayesian optimization as a guide for organic molecular metallophotocatalyst formulation discovery

Conjugated organic photoredox catalysts (OPCs) can promote a wide range of chemical transformations. It is challenging to predict the catalytic activities of OPCs from first principles, either by expert knowledge or by using a priori calculations, as catalyst activity depends on a complex range of interrelated properties. Organic photocatalysts and other catalyst systems have often been discovered by a mixture of design and trial and error. Here we report a two-step data-driven approach to the targeted synthesis of OPCs and the subsequent reaction optimization for metallophotocatalysis, demonstrated for decarboxylative sp3–sp2 cross-coupling of amino acids with aryl halides. Our approach uses a Bayesian optimization strategy coupled with encoding of key physical properties using molecular descriptors to identify promising OPCs from a virtual library of 560 candidate molecules. This led to OPC formulations that are competitive with iridium catalysts by exploring just 2.4% of the available catalyst formulation space (107 of 4,500 possible reaction conditions).

Cobalt/Photoredox Dual-Catalyzed Cross-Radical Coupling of Alkenes via Hydrogen Atom Transfer and Homolytic Substitution.

Cobalt-catalyzed metal hydride hydrogen atom transfer (MHAT) in combination with photoredox catalysis has emerged as a powerful synthetic method, owing to its redox nature and applicability to various radical precursors. Herein, we describe a cross-radical coupling reaction under cobalt/photoredox dual catalysis. MHAT and homolytic substitution (SH2) processes enabled Markovnikov-selective hydrobenzylation of di/trisubstituted alkenes, affording products with a quaternary carbon center in a redox-neutral manner.

Enantioselective Hydroaminoalkylation of Azaaryl Ketones through Asymmetric Photoredox Catalysis.

An enantioselective hydroaminoalkylation of azaaryl ketones under a transition-metal-free asymmetric photoredox catalysis platform is reported. A series of valuable azaarene-functionalized 1,2-amino alcohols featuring attractive quaternary carbon stereocenters have been synthesized in high yields with good to excellent enantioselectivities. The viability of readily accessible N-aryl glycines as reaction partners facilitates the conjugate modification of these products into important derivatives, thereby enhancing the synthetic utility of the current approach.

Photoredox Ring Opening 1,2-Alkylarylation of Alkenes with Sulfonium Salts Toward Thioether-Substituted Oxindoles.

A novel strategy for the difunctionalization of electron-deficient alkenes with aryl sulfonium salts to access remote sulfur-containing oxindole derivatives by using in situ-formed copper(I)-based complexes as a photoredox catalyst is presented. This method enables the generation of the C(sp3)-centered radicals through site selective cleavage of the C-S bond of aryl sulfonium salts under mild conditions. Moreover, the oxidation reactions of desired products provide a new strategy for the preparation of sulfoxide or sulfone-containing compounds. Importantly, this approach can be easily applied to late-stage modification of pharmaceuticals molecules.

Density functional theory‐based rapid and accurate estimation of reduction potentials of acridinium derivatives in ground and excited state

AbstractWe devised a quantum chemical simulation protocol that can rapidly and accurately predict ground and excited state reduction potentials (E0 and E*, respectively) of acridinium photoredox catalysts (PCs). To bypass time‐consuming excited state geometry optimizations, we used ground state equilibrium geometries to compute the electronic energy of excited states, which provides reasonable E0 and E* estimates. The contribution of Hartree‐Fock exchange (HFX) in density functionals was systematically varied to estimate E0 and E*. In addition to reproducing experimental results, physically sensible models, such as correct descriptions of exciton behavior, are highly necessary. Based on the exciton correlation values, the appropriate amount of HFX in the B3LYP functional was determined to be 30 % to yield physically sensible bound electron‐hole pairs for small organic molecules. We also investigated the impact of basis sets on the predictability of E0 and E*. Geometry optimizations with B3LYP‐D2(HFX 20 %)/6‐31G and single point energy refinement with (TD‐)B3LYP‐D2(HFX 30%)/6‐311++G(d,p) yielded the best results. The transferability of the suggested protocol was confirmed with a test set consisting of eight acridinium derivatives. This study can provide reasonably accurate results with relatively small amounts of computational resources, and it is therefore expected to greatly contribute to the development of new acridinium PCs.

Halogen‐Atom Transfer Enabled Catalytic Enantioselective Coupling to Chiral Trifluoromethylated Alkynes via Dual Nickel and Photocatalysis

AbstractWith halogen‐atom transfer as an effective tool, a novel catalytic enantioselective protocol to generate chiral trifluoromethylated alkynes has been established by a cooperative photoredox and nickel catalysis system, providing a straightforward and modular route to access this type of product in good yields and enantioselectivities. The halogen‐atom transfer process is essential for the reaction and this novel strategy offers another promising way to utilize alkyl halides with highly negative reduction potentials. It firstly expands nickel‐catalyzed asymmetric reductive cross‐couplings of organohalides from the traditional single‐electron transfer to halogen‐atom transfer.

Halogen-Atom Transfer Enabled Catalytic Enantioselective Coupling to Chiral Trifluoromethylated Alkynes via Dual Nickel and Photocatalysis.

With halogen-atom transfer as an effective tool, a novel catalytic enantioselective protocol to generate chiral trifluoromethylated alkynes has been established by a cooperative photoredox and nickel catalysis system, providing a straightforward and modular route to access this type of product in good yields and enantioselectivities. The halogen-atom transfer process is essential for the reaction and this novel strategy offers another promising way to utilize alkyl halides with highly negative reduction potentials. It firstly expands nickel-catalyzed asymmetric reductive cross-couplings of organohalides from the traditional single-electron transfer to halogen-atom transfer.

A Review on Piezoelectric-mediated Mechanoredox Reactions by Ball Milling in Organic Synthesis

Abstract: Recently, the concept of mechanoredox chemistry has been proposed and welldeveloped in organic synthesis. Mechanoredox chemistry is conceptually similar to a photocatalyst reaction system, where piezoelectric materials are introduced to the reaction system in a manner analogous to photoredox catalysis. These reactions feature the ability to generate high-value radicals that do not require harsh reaction conditions of anhydrous and anaerobic conditions, an expensive photocatalyst, and the use of solvents, which renders these transformations highly industrially applicable. In addition, mechanoredox chemistry is also an emerging interdisciplinary research field that combines material chemistry with synthetic chemistry to create more useful reactions. This review provides a comprehensive summary of progress to date in the specific transformation and related mechanisms of piezoelectric- mediated mechanoredox reactions by ball milling in organic synthesis.

Redox reactivity of LMCT and MLCT excited states of Earth‐abundant metal complexes

AbstractPrecious metal complexes, which act as excellent photoredox catalysts, have now being replaced by earth‐abundant metal complexes. This review focused on redox reactivity of ligand‐to‐metal charge transfer (LMCT) and metal‐to‐ligand charge transfer (MLCT) excited states of earth‐abundant metal complexes. Iron complexes with strongly σ‐donating NHC‐ligands (NHC = N‐heterocyclic carbene) has emerged, featuring long lived LMCT excited states due to a significantly increased barrier for deactivation via metal centered states. A Fe(III)‐NHC complex acts as an effective photoredox catalyst for various photocatalytic redox reactions. Although manganese(IV)‐oxo complexes have no long‐lived excited states (τ < < 1 ns). Once acids such as Sc(OTf)3 and HOTf are bound to the oxo moiety of Mn(IV)‐oxo complexes, the photoexcitation of acid‐bound Mn(IV)‐oxo complexes resulted in formation of the excited states with microseconds lifetimes, which are capable of oxidation of substrates including benzene to phenol. Photoexcited states of Mn(III), Mn(II) and Mn(I) complexes act as photoreductants to reduce substrates including O2. On the other hand, photoexcited states of Co(IV) and Co(III) complexes act as photooxidants, whereas those of Co(II) and Co(I) complexes act as photoreductants. With regard to the excited state lifetime, [Cr(tpe)2]3+ (tpe = 1,1,1‐tris(pyrid‐2‐yl)ethane) exhibited the longest luminescence lifetime (τ = 4500 μs), acting as an effective photoredox catalyst for photocatalytic redox reactions. The LMCT state of a Cr(0) complex acts as a super photoreductant. Thus, LMCT and MLCT excited states of earth‐abundant metal complexes are utilized as strong photooxidants and photoreductants, respectively.

Photoredox Catalyzed Synthesis of gem-Difluoroalkenes and Monofluorinated Cyclooctenes via 1,5-HAT Process.

gem-Difluoroalkenes and monofluorinated cycloalkenes have emerged as basic structural units in a variety of bioactive molecules and natural products. Thus, developing straightforward and efficient methods for synthesizing fluorinated alkene compounds is of considerable significance. Herein, we disclose a visible-light-induced defluorination of 2-trifluoromethyl-1-alkene via a 1,5-HAT process using N-alkoxyphtalimides as both radical precursor and potential nucleophile. The mild and stepwise reaction leads to a variety of structurally diverse gem-difluoroalkenes and monofluorinated cyclooctenes with high efficiency, respectively.

Bicyclo[1.1.0]butyl Radical Cations: Synthesis and Application to [2π+2σ] Cycloaddition Reactions.

As the chemistry that surrounds the field of strained hydrocarbons, such as bicyclo[1.1.0]butane, continues to expand, it becomes increasingly advantageous to develop alternative reactivity modes that harness their unique properties to access new regions of chemical space. Herein, we report the use of photoredox catalysis to promote the single-electron oxidation of bicyclo[1.1.0]butanes. The synthetic utility of the resulting radical cations is highlighted by their ability to undergo highly regio- and diastereoselective [2π + 2σ] cycloaddition reactions. The most notable feature of this transformation is the breadth of alkene classes that can be employed, including nonactivated alkenes, which have so far been elusive for previous strategies. A rigorous mechanistic investigation, in conjunction with DFT computation, was undertaken in order to better understand the physical nature of bicyclo[1.1.0]butyl radical cations and thus provides a platform from which further studies into the synthetic applications of these intermediates can be built upon.

Mechanisms of Photoredox Catalysis Featuring Nickel-Bipyridine Complexes.

Metallaphotoredox catalysis can unlock useful pathways for transforming organic reactants into desirable products, largely due to the conversion of photon energy into chemical potential to drive redox and bond transformation processes. Despite the importance of these processes for cross-coupling reactions and other transformations, their mechanistic details are only superficially understood. In this review, we have provided a detailed summary of various photoredox mechanisms that have been proposed to date for Ni-bipyridine (bpy) complexes, focusing separately on photosensitized and direct excitation reaction processes. By highlighting multiple bond transformation pathways and key findings, we depict how photoredox reaction mechanisms, which ultimately define substrate scope, are themselves defined by the ground- and excited-state geometric and electronic structures of key Ni-based intermediates. We further identify knowledge gaps to motivate future mechanistic studies and the development of synergistic research approaches spanning the physical, organic, and inorganic chemistry communities.

Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis.

Organic photocatalysts frequently possess dual singlet and triplet photoreactivity and a thorough photochemical characterization is essential for efficient light-driven applications. In this article, the mode of action of a polyazahelicene catalyst (Aza-H) was investigated using laser flash photolysis (LFP). The study revealed that the chromophore can function as a singlet-state photoredox catalyst in the sulfonylation/arylation of styrenes and as a triplet sensitizer in energy transfer catalysis. The singlet lifetime is sufficiently long to exploit the exceptional excited state reduction potential for the activation of 4-cyanopyridine. Photoinduced electron transfer generating the radical cation was directly observed confirming the previously proposed mechanism of a three-component reaction. Several steps of the photoredox cycle were investigated separately, providing deep insights into the complex mechanism. The triplet-excited Aza-H, which was studied with quantitative LFP, is formed with a quantum yield of 0.34. The pronounced triplet formation was exploited for the isomerization reaction of (E)-stilbene to the Z-isomer and the cyclization of cinnamyl chloride. Catalyst degradation mainly occurs through the long-lived Aza-H triplet (28 µs), but the photostability is greatly increased when the triplet efficiently reacts in a catalytic cycle such that turnover numbers exceeding 4400 are achievable with this organocatalyst.