Deconstructive Carboxylation of Activated Alkenes with Carbon Dioxide.

Carboxylation with carbon dioxide (CO2 ) represents one notable methodology to produce carboxylic acids. In contrast to carbon-heteroatom bonds, carbon-carbon bond cleavage for carboxylation with CO2 is far more challenging due to their inherent and less favorable orbital directionality for interacting with transition metals. Here we report a photocatalytic protocol for the deconstructive carboxylation of alkenes with CO2 to generate carboxylic acids in the absence of transition metals. It is emphasized that our protocol provides carboxylic acids with obviously unchanged carbon numbers when terminal alkenes were used. To show the power of this strategy, a variety of pharmaceutically relevant applications including the modular synthesis of propionate nonsteroidal anti-inflammatory drugs and the late-stage carboxylation of bioactive molecule derivatives are demonstrated.

Aroyl Fluorides as Bifunctional Reagents for Dearomatizing Fluoroaroylation of Benzofurans.

The 2,3-dihydrobenzofuran scaffold is widely found in natural products and biologically active compounds. Herein, dearomatizing 2,3-fluoroaroylation of benzofurans with aroyl fluorides as bifunctional reagents to access 2,3-difunctionalized dihydrobenzofurans is reported. The reaction that occurs by cooperative NHC/photoredox catalysis provides 3-aroyl-2-fluoro-2,3-dihydrobenzofurans with moderate to good yield and high diastereoselectivity. Cascades proceed via radical/radical cross-coupling of a benzofuran radical cation generated in the photoredox catalysis cycle with a neutral ketyl radical formed through the NHC catalysis cycle. The redox-neutral transformation exhibits broad substrate scope and high functional group compatibility. With anhydrides as bifunctional reagents, dearomatizing aroyloxyacylation of benzofurans is achieved and the strategy can also be applied to N-acylated indoles to afford 3-aroyl-2-fluoro-dihydroindoles.

Cooperative NHC and Photoredox Catalysis for the Synthesis of ß-Trifluoromethylated Alkyl Aryl Ketones.

Despite the great potential of radical chemistry in organic synthesis, N-heterocyclic carbene (NHC)-catalyzed reactions involving radical intermediates are not well explored. This communication reports the three-component coupling of aroyl fluorides, styrenes and the Langlois reagent (CF3 SO2 Na) to give various ß-trifluoromethylated alkyl aryl ketones with good functional group tolerance in moderate to high yields by cooperative photoredox/NHC catalysis. The alkene acyltrifluoromethylation proceeds via radical/radical cross coupling of ketyl radicals with benzylic C-radicals. The ketyl radicals are generated via SET reduction of in situ formed acylazolium ions whereas the benzylic radicals derive from trifluoromethyl radical addition onto styrenes.

Photocarboxylation of Benzylic C-H Bonds.

The carboxylation of sp3-hybridized C-H bonds with CO2 is a challenging transformation. Herein, we report a visible-light-mediated carboxylation of benzylic C-H bonds with CO2 into 2-arylpropionic acids under metal-free conditions. Photo-oxidized triisopropylsilanethiol was used as the hydrogen atom transfer catalyst to afford a benzylic radical that accepts an electron from the reduced form of 2,3,4,6-tetra(9H-carbazol-9-yl)-5-(1-phenylethyl)benzonitrile generated in situ. The resulting benzylic carbanion reacts with CO2 to generate the corresponding carboxylic acid after protonation. The reaction proceeded without the addition of any sacrificial electron donor, electron acceptor or stoichiometric additives. Moderate to good yields of the desired products were obtained in a broad substrate scope. Several drugs were successfully synthesized using the novel strategy.

Site-Selective, Remote sp3 C-H Carboxylation Enabled by the Merger of Photoredox and Nickel Catalysis.

A photoinduced carboxylation of alkyl halides with CO2 at remote sp3 C-H sites enabled by the merger of photoredox and Ni catalysis is described. This protocol features a predictable reactivity and site selectivity that can be modulated by the ligand backbone. Preliminary studies reinforce a rationale based on a dynamic displacement of the catalyst throughout the alkyl side chain.

Controllable Isomerization of Alkenes by Dual Visible-Light-Cobalt Catalysis.

We report herein that thermodynamic and kinetic isomerization of alkenes can be accomplished by the combination of visible light with Co catalysis. Utilizing Xantphos as the ligand, the most stable isomers are obtained, while isomerizing terminal alkenes over one position can be selectively controlled by using DPEphos as the ligand. The presence of the donor-acceptor dye 4CzIPN accelerates the reaction further. Transformation of exocyclic alkenes into the corresponding endocyclic products could be efficiently realized by using 4CzIPN and Co(acac)2 in the absence of any additional ligands. Spectroscopic and spectroelectrochemical investigations indicate CoI being involved in the generation of a Co hydride, which subsequently adds to alkenes initiating the isomerization.

Boosting Electrochemical Reduction of CO2 at a Low Overpotential by Amorphous Ag-Bi-S-O Decorated Bi0 Nanocrystals.

Bimetal-S-O composites have been rarely researched in electrochemical reduction of CO2 . Now, an amorphous Ag-Bi-S-O decorated Bi0 catalyst derived from Ag0.95 BiS0.75 O3.1 nanorods by electrochemical pre-treatment was used for catalyzing eCO2 RR, which exhibited a formate FE of 94.3 % with a formate partial current density of 12.52 mA cm-2 at an overpotential of only 450 mV. This superior performance was attributed to the attached amorphous Ag-Bi-S-O substance. S could be retained in the amorphous region after electrochemical pre-treatment only in samples derived from metal-S-O composites, and it would greatly enhance the formate selectivity by accelerating the dissociation of H2 O. The existence of Ag would increase the current density, resulting in a higher local pH, which made the role of S in activating H2 O more significantly and suppressed H2 evolution more effectively, thus endowing the catalyst with a higher formate FE at low overpotentials.

Ligand-Controlled Regioselective Hydrocarboxylation of Styrenes with CO2 by Combining Visible Light and Nickel Catalysis.

The ligand-controlled Markovnikov and anti-Markovnikov hydrocarboxylation of styrenes with atmospheric pressure of CO2 at room temperature using dual visible-light-nickel catalysis has been developed. In the presence of neocuproine as ligand, the Markovnikov product is obtained exclusively, while employing 1,4-bis(diphenylphosphino)butane (dppb) as the ligand favors the formation of the anti-Markovnikov product. A range of functional groups and electron-poor, -neutral, as well as electron-rich styrene derivatives are tolerated by the reaction, providing the desired products in moderate to good yields. Preliminary mechanistic investigations indicate the generation of a nickel hydride (H-NiII) intermediate, which subsequently adds irreversibly to styrenes.

Carboxylation of Aromatic and Aliphatic Bromides and Triflates with CO2 by Dual Visible-Light-Nickel Catalysis.

We report the efficient carboxylation of bromides and triflates with K2 CO3 as the source of CO2 in the presence of an organic photocatalyst in combination with a nickel complex under visible light irradiation at room temperature. The reaction is compatible with a variety of functional groups and has been successfully applied to the synthesis and derivatization of biologically active molecules. In particular, the carboxylation of unactivated cyclic alkyl bromides proceeded well with our protocol, thus extending the scope of this transformation. Spectroscopic and spectroelectrochemical investigations indicated the generation of a Ni0 species as a catalytic reactive intermediate.

Photocatalysis with Quantum Dots and Visible Light: Selective and Efficient Oxidation of Alcohols to Carbonyl Compounds through a Radical Relay Process in Water.

Selective oxidation of alcohols to aldehydes/ketones has been achieved with the help of 3-mercaptopropionic acid (MPA)-capped CdSe quantum dot (MPA-CdSe QD) and visible light. Visible-light-prompted electron-transfer reaction initiates the oxidation. The thiyl radical generated from the thiolate anion adsorbed on a CdSe QD plays a key role by abstracting the hydrogen atom from the C-H bond of the alcohol (R1 CH(OH)R2 ). The reaction shows high efficiency, good functional group tolerance, and high site-selectivity in polyhydroxy compounds. The generality and selectivity reported here offer a new opportunity for further applications of QDs in organic transformations.

General and Efficient Intermolecular [2+2] Photodimerization of Chalcones and Cinnamic Acid Derivatives in Solution through Visible-Light Catalysis.

[2+2] Photocycloaddition, for example, the dimerization of chalcones and cinnamic acid derivatives, is a unique strategy to construct cyclobutanes, which are building blocks for a variety of biologically active molecules and natural products. However, most attempts at the above [2+2] addition have focused on solid-state, molten-state, or host-guest systems under ultraviolet-light irradiation in order to overcome the competition of facile geometric isomerization of nonrigid olefins. We report a general and simple method to realize the intermolecular [2+2] dimerization reaction of these acyclic olefins to construct cyclobutanes in a highly regio- and diastereoselective manner in solution under visible light, which provides an efficient solution to a long-standing problem.

Photocatalytic Hydrogen-Evolution Cross-Couplings: Benzene C-H Amination and Hydroxylation.

We present a blueprint for aromatic C-H functionalization via a combination of photocatalysis and cobalt catalysis and describe the utility of this strategy for benzene amination and hydroxylation. Without any sacrificial oxidant, we could use the dual catalyst system to produce aniline directly from benzene and ammonia, and phenol from benzene and water, both with evolution of hydrogen gas under unusually mild conditions in excellent yields and selectivities.

Radical Addition of Hydrazones by α-Bromo Ketones To Prepare 1,3,5-Trisubstituted Pyrazoles via Visible Light Catalysis.

A novel efficient tandem reaction of hydrazones and α-bromo ketones is reported for the preparation of 1,3,5-trisubstituted pyrazoles by visible light catalysis. In this system, the monosubstituted hydrazones show wonderful reaction activity with alkyl radicals, generated from α-bromo ketones. A radical addition followed by intramolecular cyclization affords the important pyrazole skeleton in good to excellent yields. This efficient strategy under mild conditions with wide group tolerance provides a potential approach to the 1,3,5-trisubstituted pyrazoles.

Activation of CH Bonds through Oxidant-Free Photoredox Catalysis: Cross-Coupling Hydrogen-Evolution Transformation of Isochromans and ß-Keto Esters.

The direct and controlled activation of a C(sp(3) )H bond adjacent to an O atom is of particular synthetic value for the conventional derivatization of ethers or alcohols. In general, stoichiometric amounts of an oxidant are required to remove an electron and a hydrogen atom of the ether for subsequent transformations. Herein, we demonstrate that the activation of a CH bond next to an O atom could be achieved under oxidant-free conditions through photoredox-neutral catalysis. By using a commercial dyad photosensitizer (Acr(+) -Mes ClO4 (-) , 9-mesityl-10-methylacridinium perchlorate) and an easily available cobaloxime complex (Co(dmgBF2 )2 ⋅2 MeCN, dmg=dimethylglyoxime), the nucleophilic addition of ß-keto esters to oxonium species, which is rarely observed in photocatalysis, leads to the corresponding coupling products and H2 in moderate to good yields under visible-light irradiation. Mechanistic studies suggest that both isochroman and the cobaloxime complex quench the electron-transfer state of this dyad photosensitizer and that benzylic CH bond cleavage is probably the rate-determining step of this cross-coupling hydrogen-evolution transformation.

Visible light catalysis-assisted assembly of Ni(h)-QD hollow nanospheres in situ via hydrogen bubbles.

Hollow spheres are one of the most promising micro-/nanostructures because of their unique performance in diverse applications. Templates, surfactants, and structure-directing agents are often used to control the sizes and morphologies of hollow spheres. In this Article, we describe a simple method based on visible light catalysis for preparing hollow nanospheres from CdE (E = Te, Se, and S) quantum dots (QDs) and nickel (Ni(2+)) salts in aqueous media. In contrast to the well-developed traditional approaches, the hollow nanospheres of QDs are formed in situ by the photogeneration of hydrogen (H2) gas bubbles at room temperature. Each component, that is, the QDs, metal ions, ascorbic acid (H2A), and visible light, is essential for the formation of hollow nanospheres. The quality of the hollow nanospheres depends on the pH, metal ions, and wavelength and intensity of visible light used. Of the various metal ions investigated, including Cu(+), Cu(2+), Fe(2+), Fe(3+), Ni(2+), Mn(2+), RuCl5(2-), Ag(+), and PtCl4(2-), Ni(2+) ions showed the best ability to generate H2 and hollow-structured nanospheres under visible light irradiation. The average diameter and shell thickness of the nanospheres ranged from 10 to 20 nm and from 3 to 6 nm, respectively, which are values rarely reported in the literature. Studies using high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), inductively coupled plasma-mass spectroscopy (ICP-AES), and steady-state and time-resolved spectroscopy revealed the chemical nature of the hollow nanospheres. Additionally, the hollow-structured nanospheres exhibit excellent photocatalytic activity and stability for the generation of H2 with a rate constant of 21 µmol h(-1) mg(-1) and a turnover number (TON) of 137,500 or 30,250 for CdTe QDs or nickel, respectively, under visible light irradiation for 42 h.

Mechanistic insights into the interface-directed transformation of thiols into disulfides and molecular hydrogen by visible-light irradiation of quantum dots.

Quantum dots (QDs) offer new and versatile ways to harvest light energy. However, there are few examples involving the utilization of QDs in organic synthesis. Visible-light irradiation of CdSe QDs was found to result in virtually quantitative coupling of a variety of thiols to give disulfides and H2 without the need for sacrificial reagents or external oxidants. The addition of small amounts of nickel(II) salts dramatically improved the efficiency and conversion through facilitating the formation of hydrogen atoms, thereby leading to faster regeneration of the ground-state QDs. Mechanistic studies reveal that the coupling reaction occurs on the QD surfaces rather than in solution and offer a blueprint for how these QDs may be used in other photocatalytic applications. Because no sacrificial agent or oxidant is necessary and the catalyst is reusable, this method may be useful for the formation of disulfide bonds in proteins as well as in other systems sensitive to the presence of oxidants.

Intramolecular Dehydrogenative Photocyclization of N-Phenyl-1-naphthamides.

Here, we explore a dehydrogenative 6π photocyclization method for N-substituted naphthalene carboxamides, which can be conducted in air. This method employs DMSO as both the reaction solvent and oxidant while also stabilizing the excited state of the substrate. Furthermore, the addition of photosensitizer enables the reaction to proceed under a 440-445 nm LED source via energy transfer. The proposed mechanism is initially validated through DFT calculations.

A cascade cross-coupling hydrogen evolution reaction by visible light catalysis.

Cross-dehydrogenative-coupling reaction has long been recognized as a powerful tool to form a C-C bond directly from two different C-H bonds. Most current processes are performed by making use of stoichiometric amounts of oxidizing agents. We describe here a new type of reaction, namely cross-coupling hydrogen evolution (CCHE), with no use of any sacrificial oxidants, and only hydrogen (H2) is generated as a side product. By combining eosin Y and a graphene-supported RuO2 nanocomposite (G-RuO2) as a photosensitizer and a catalyst, the desired cross-coupling products and H2 are achieved in quantitative yields under visible light irradiation at room temperature.

A highly efficient and selective aerobic cross-dehydrogenative-coupling reaction photocatalyzed by a platinum(II) terpyridyl complex.

Thanks to the superior redox potential of platinum(II) complex compared with that of Ru(bpy)3(2+) in the excited state, an efficient and selective visible-light-induced CDC reaction has been developed by using a catalytic amount (0.25 %) of 1. With the aid of FeSO4 (2 equiv), the corresponding amide could not be detected under visible-light irradiation (λ=450 nm), but the desired cross-coupling product was exclusively obtained under ambient air conditions. A spectroscopic study and product analysis revealed that the CDC reaction is initiated by photoinduced electron-transfer from N-phenyltetrahydroisoquinoline to the complex. An EPR (electron paramagnetic resonance) experiment provides direct evidence on the generation of superoxide radical anion (O2(-·)) rather than singlet oxygen ((1)O2) under irradiation of the reaction system, in contrast to that reported in the literature. Combined, the photoinduced electron-transfer and subsequent formation of superoxide radical anion (O2(-·)) results in a clean and facile transformation.

[Essence of SUN Shen-tian's clinical features on acupuncture and moxibustion].

To summarize SUN Shen-tian's treatment ideas and clinical features. SUN applies meridian syndrome differentiation to the diagnosis and treatment of diseases; advocates that prevention and treatment of diseases should be regulated mind firstly; applies transcranial repetitive acupuncture combined modern cerebral cortex function positioning; emphasizes the application of multiple acupuncture methods and manipulation, and includes the meridian penetrating needling method, the flat needling and penetrating needling method, and the stagnant needle lifting method, pays attention to the importance of achieving qi and manipulation for the effect.