Photoredox Catalysis Research Articles

Nickel-Photoredox-Catalyzed Stereoconvergent Coupling of Alkenyl Halides and Nitrogen-Containing Heterocycles.

Nitrogen-containing heterocycles possessing N-alkenyl substituents are an important structural motif. However, the synthetic methods reported thus far cannot selectively synthesize the Z stereoisomer on the basis of the stereochemistry of the substituted alkenes. Herein, we report the stereoconvergent coupling of heterocycles and alkenyl halides consisting of a mixture of E/Z stereoisomers, which selectively afforded the thermodynamically less stable Z-coupling product. Mechanistic studies suggest that a nickel photoredox catalyst facilitates the formation of N-centered heteroarene radicals.

C–heteroatom coupling with electron-rich aryls enabled by nickel catalysis and light

Nickel photoredox catalysis has resulted in a rich development of transition-metal-catalysed transformations for carbon–heteroatom bond formation. By harnessing light energy, the transition metal can attain oxidation states that are difficult to achieve through thermal chemistry in a catalytic manifold. For example, nickel photoredox reactions have been reported for both the synthesis of anilines and aryl ethers from aryl(pseudo)halides. However, oxidative addition to simple nickel systems is often sluggish in the absence of special, electron-rich ligands, leading to catalyst decomposition. Electron-rich aryl electrophiles therefore currently fall outside the scope of many transformations in the field. Here we provide a conceptual solution to this problem and demonstrate nickel-catalysed C–heteroatom bond-forming reactions of arylthianthrenium salts, including amination, oxygenation, sulfuration and halogenation. Because the redox properties of arylthianthrenium salts are primarily dictated by the thianthrenium, oxidative addition of highly electron-rich aryl donors can be unlocked using simple NiCl2 under light irradiation to form the desired C‒heteroatom bonds.

Novel Photocatalyst Based on Through‐Space Charge Transfer Induced Intersystem Crossing Enables Rapid and Efficient Polymerization Under Low‐Power Excitation Light

AbstractCurrently, most photoredox catalysis polymerization systems are limited by high excitation power, long polymerization time, or the requirement of electron donors due to the precise design of efficient photocatalysts still poses a great challenge. Herein, we propose a new approach: the creation of efficient photocatalysts having low ground state oxidation potentials and high excited state energy levels, along with through‐space charge transfer (TSCT) induced intersystem crossing (ISC) properties. A cabazole‐naphthalimide (NI) dyad (NI‐1) characterized by long triplet excited state lifetime (τT=62 μs), satisfactory ISC efficiency (ΦΔ=54.3 %) and powerful reduction capacity [Singlet: E1/2 (PC+1/*PC)=−1.93 eV, Triplet: E1/2 (PC+1/*PC)=−0.84 eV] was obtained. An efficient and rapid polymerization (83 % conversion of 1 mM monomer in 30 s) was observed under the conditions of without electron donor, low excitation power (10 mW cm−2) and low catalyst (NI‐1) loading (<50 μM). In contrast, the conversion rate was lower at 29 % when the reference catalyst (NI‐4) was used for photopolymerization under the same conditions, demonstrating the advantage of the TSCT photocatalyst. Finally, the TSCT material was used as a photocatalyst in practical lithography for the first time, achieving pattern resolutions of up to 10 μm.

Direct C(sp3)-H functionalization with thiosulfonates via photoredox catalysis

While C(sp3)-S bonds exist in many biologically active compounds, the direct catalytic C(sp3)-H thiolation remains elusive. Herein, we report a convenient and green C(sp3)-H thiolation approach mediated by using tetrabutylammonium decatungstate (TBADT) as a hydrogen atom transfer (HAT) photocatalyst. A wide range of C(sp3)-H bond-containing etheric, allylic, alkyl, ketonic, amidic substrates and sulfonyl-based SOMOphiles participated in the reaction, producing thioethers with high efficiency. The present protocol features green characteristics, such as being free of harmful oxidants and additives; step-economic; redox-neutral; and amenable to scale-up assisted by continuous-flow technology.

Stereoselective amino acid synthesis by photobiocatalytic oxidative coupling.

Photobiocatalysis-where light is used to expand the reactivity of an enzyme-has recently emerged as a powerful strategy to develop chemistries that are new to nature. These systems have shown potential in asymmetric radical reactions that have long eluded small-molecule catalysts1. So far, unnatural photobiocatalytic reactions are limited to overall reductive and redox-neutral processes2-9. Here we report photobiocatalytic asymmetric sp3-sp3 oxidative cross-coupling between organoboron reagents and amino acids. This reaction requires the cooperative use of engineered pyridoxal biocatalysts, photoredox catalysts and an oxidizing agent. We repurpose a family of pyridoxal-5'-phosphate-dependent enzymes, threonine aldolases10-12, for the α-C-H functionalization of glycine and α-branched amino acid substrates by a radical mechanism, giving rise to a range of α-tri- and tetrasubstituted non-canonical amino acids 13-15 possessing up to two contiguous stereocentres. Directed evolution of pyridoxal radical enzymes allowed primary and secondary radical precursors, including benzyl, allyl and alkylboron reagents, to be coupled in an enantio- and diastereocontrolled fashion. Cooperative photoredox-pyridoxal biocatalysis provides a platform for sp3-sp3 oxidative coupling16, permitting the stereoselective, intermolecular free-radical transformations that are unknown to chemistry or biology.

Metal-Free Photoredox Catalyzed Sulfonylation of Phenylhydrazines with Thiols.

The sulfonylation method stands out as a simple and efficient approach for synthesizing sulfonamides. Despite the advancements in constructing the sulfonamide framework, the potential use of phenyl hydrazine as an amination source remains unexplored. Herein, we report a metal-free, environment-friendly photoredox-catalyzed sulfonylation of phenylhydrazines using thiols, employing MeCN:H2O as a green solvent and eosin Y as a photoredox catalyst. This strategy exhibits a broad substrate scope and good functional group compatibility, including hetero(aryl) as well as aliphatic phenylhydrazines. Finally, this protocol also demonstrated good application for the synthesis of pharmaceutical analogues.

Mild Strategy for the Preparation of Alkyl Sulfonyl Fluorides from Alkyl Bromides and Alcohols Using Photoredox Catalysis and Flow Chemistry.

Facile access to sp3-rich scaffolds containing a sulfonyl fluoride group is still limited. Herein, we describe a mild and scalable strategy for the preparation of alkyl sulfonyl fluorides from readily available alkyl bromides and alcohols using photoredox catalysis. This approach is based on halogen atom transfer (XAT), followed by SO2 capture and fluorination. The method features mild conditions enabling fast access to high-value derivatives and has been scaled up to 5 g using a continuous stirred tank reactor cascade.

Efficient Functionalization of Organosulfones via Photoredox Catalysis: Direct Incorporation of α-Carbonyl Alkyl Side Chains into α-Allyl-β-Ketosulfones.

A novel and efficient method for functionalizing organosulfones has been established, utilizing a visible-light-driven intermolecular radical cascade cyclization of α-allyl-β-ketosulfones. This process employs fac-Ir(ppy)3 as the photoredox catalyst and α-carbonyl alkyl bromide as the oxidizing agent. Via this approach, the substrates experience intermolecular addition of α-carbonyl alkyl radicals to the alkene bonds, initiating a sequence of C-C bond formations that culminate in the production of organosulfone derivatives. Notably, this technique features gentle reaction conditions and an exceptional compatibility with a wide array of functional groups, making it a versatile and valuable addition to the field of organic synthesis.

N‐Directed defluorinative γ‐C(sp3)−H allylation of sulfamate esters for synthesis of gem‐difluoroalkenes via photoredox catalysis

Abstractgem‐Difluoroalkenes are unique structural motifs with important applications ranging from drugs to materials. Herein, we report a novel radical‐mediated defluorinative allylation of sulfamate esters with through distal C(sp3)−H functionalization under photoredox conditions. The reaction could readily incorporate various gem‐difluoroalkene motifs into previously unfunctionalized sp3 carbon centers. The transformation allows directly dual activation of N−H and C(sp3)−H bonds via a photocatalytic and redox‐neutral process, as well as using water as environmentally friendly co‐solvent. The reaction could provide a general and operationally simple method to access gem‐difluoroalkene compounds with high diversity.

10-Phenylphenothiazine-Organophotocatalyzed Bromo-Perfluoroalkylation of Unactivated Olefins.

In this study, we have developed a smooth metal-free visible-light-induced bromo-perfluoroalkylation of unactivated olefins with the aid of 10-phenylphenothiazine (PTH) as an organic photoredox catalyst. The reaction is 100% atom-economic redox-neutral and proceeds with stoichiometric amounts of olefin and perfluoroalkyl bromide. To show the potential of these unexplored motifs, we carried out various postfunctionalizations taking advantage of the bromine atom, including gram-scale experiments.

Deoxy-Arylation of Amides via a Tandem Hydrosilylation/Radical- Radical Coupling Sequence.

Vaska's complex is a prominent catalyst for the hydrosilylation of amides. The O-silyl hemiaminal intermediate formed in these processes has been demonstrated as an electrophile for nucleophilic additions. More recently, these intermediates have been shown to be suitable for single electron reduction to generate α-amino radicals. Leveraging the ability to generate α-amino radicals from these hemiaminals, we describe a two-step, one-pot, deoxy-arylation of amides utilizing iridium-catalyzed hydrosilylation and photoredox catalysis. This transformation can be tailored toward the late-stage functionalization of biologically relevant molecules, with drug discovery applications as shown in the streamlined synthesis of an NPY Y2 inhibitor.

Tuning Photoredox Catalysis of Ruthenium with Palladium: Synthesis of Heterobimetallic Ru-Pd Complexes That Enable Efficient Photochemical Reduction of CO2.

New Ru-Pd heterobimetallic complexes were synthesized and structurally characterized utilizing 6,6″-bis(phosphino)-2,2':6',2″-terpyridine as a scaffold for the metal-metal bond. The dicationic Ru-Pd complex was found to exhibit high catalytic activity as a photocatalyst for photochemical reduction of CO2 to CO under visible light irradiation. This study established a new design of transition metal catalysts that tune photoredox catalysis with metalloligands.

Protocol for the Photocatalytic Hydroxyalkenylation of Alkenes Using 1,2‐Bis(phenylsulfonyl)ethylene and Water

AbstractWe report on a protocol for the hydroxyalkenylation of alkenes using an acridinium photoredox catalyst in combination with 1,2‐bis(phenylsulfonyl)ethylene and water. Using the protocol, alkenes could be converted into the corresponding 1‐phenylsulfonyl‐4‐hydroxyalkenes in good yields. The hydroxyalkenylation involves the nucleophilic hydroxylation of alkene‐derived radical cations to give β‐hydroxyalkyl radicals, which then undergo a radical addition/β‐elimination sequence. The catalytic cycle is likely sustained by electron transfer from the acridine radical to the benzenesulfonyl radical, which is formed via a radical addition/elimination sequence.

Hydrofluorination of Alkenes Using Et3N·HF under Dual Cobalt and Photoredox Catalysis

Hydrofluorination of Alkenes Using Et3N·HF under Dual Cobalt and Photoredox Catalysis

Dialkylation of Alkenes with Aliphatic Alcohols and Alkyl Halides by Dual Nickel and Photoredox Catalysis

Dialkylation of Alkenes with Aliphatic Alcohols and Alkyl Halides by Dual Nickel and Photoredox Catalysis

Hydrohalogenation of Alkenes Using Collidine·HX Salts under Dual Cobalt and Photoredox Catalysis

Hydrohalogenation of Alkenes Using Collidine·HX Salts under Dual Cobalt and Photoredox Catalysis

Aerobic Photoredox Catalyzed Oxamate Ester Synthesis from Bromodifluoroacetate Esters

AbstractHere we report an aerobic photoredox catalysis approach to oxamate ester synthesis using bromodifluoroacetate esters and amines under open‐air conditions. Oxamate ester is an important skeleton found in bioactive molecules and used as a synthetic building block. However, previous synthetic methods require the use of moisture‐ and air‐sensitive precursors and/or harsh conditions, limiting accessible oxamate esters. The present method uses bench‐stable bromodifluoroacetate esters and amines under mild photoredox catalytic conditions to furnish a wide variety of oxamate esters. Combining photoredox catalysis with aerobic oxygenation enables the use of bromodifluoroacetate ester as a precursor for the synthesis of oxamate esters via fluoroglyoxylate esters.

Synthesis of Artemisinin G from Artemisinin via Photocatalysis

AbstractPhotoredox catalysis has become a mainstay in synthetic methodology over the past decade. However, its application in the functionalization of natural products remains to be further explored. Herein, we report an efficient approach to synthesize artemisinin G from artemisinin via photocatalysis in high yield.

Catalytic Photoredox Carbobromination of Unactivated Alkenes with α-Bromocarbonyls via the Mechanistically Distinct Radical-Addition Radical-Pairing Pathway

Catalytic Photoredox Carbobromination of Unactivated Alkenes with α-Bromocarbonyls via the Mechanistically Distinct Radical-Addition Radical-Pairing Pathway

Selective Mono-Defluorinative Cross-Coupling of Trifluoromethyl arenes via Multiphoton Photoredox Catalysis.

A new cross-coupling of trifluoromethyl arenes has been realized via multiphoton photoredox catalysis. Trifluoromethyl arenes were demonstrated to undergo selective mono-defluorinative alkylation under mild reaction conditions providing access to a series of valuable α,α-difluorobenzylic compounds. The reaction shows broad substrate scope and general functional group tolerance. In addition to the electron-deficient trifluoromethyl arenes that are easily reduced to the corresponding radical anion, more challenging electron-rich substrates were also successfully applied. Steady-State Stern-Volmer quenching studies indicated that the trifluoromethyl arenes were reduced by the multiphoton excited Ir-based photocatalyst.