Direct Mechanism of the First Carbon–Carbon Bond Formation in the Methanol‐to‐Hydrocarbons Process

In the past two decades, the reaction mechanism of C−C bond formation from either methanol or dimethyl ether (DME) in the methanol‐to‐hydrocarbons (MTH) process has been a highly controversial issue. Described here is the first observation of a surface methyleneoxy analogue, originating from the surface‐activated DME, by in situ solid‐state NMR spectroscopy, a species crucial to the first C−C bond formation in the MTH process. New insights into the first C−C bond formation were provided, thus suggesting DME/methanol activation and direct C−C bond formation by an interesting synergetic mechanism, involving C−H bond breakage and C−C bond coupling during the initial methanol reaction within the chemical environment of the zeolite catalyst.     

PdII‐Catalyzed Regio‐ and Enantioselective Oxidative C−H/C−H Cross‐Coupling Reaction between Ferrocenes and Azoles

Asymmetric C?H bond functionalization reaction is one of the most efficient and straightforward methods for the synthesis of optically active molecules. Herein we disclose an asymmetric C?H/C?H cross‐coupling reaction of ferrocenes with azoles such as oxazoles and thiazoles. Palladium(II)/monoprotected amino acid (MPAA) catalytic system which exhibits excellent reactivity and regioselectivity for oxazoles and thiazoles. This method offers a powerful strategy for constructing planar chiral ferrocenes. Mechanistic studies suggest that the C?H bond cleavage of azoles is likely proceeding through a S_EAr process and may not be a turnover limiting step.     

Copper‐Catalyzed One‐Pot Denitrogenative–Dehydrogenative–Decarboxylative Coupling of β‐Ketoacids with Trifluorodiazoethane: Facile Access to Trifluoromethylated Aldol Products

A novel copper‐catalyzed one‐pot cross‐coupling of β‐ketoacids with in situ generated trifluorodiazoethane has been developed. This reaction provides a direct and efficient method, in which one C?C bond and one C?O bond were formed in a carbenoid center with concomitant denitrogenation–dehydrogenation–decarboxylation, to afford trifluoromethylated aldol products. In several preliminary experiments, good to high enantioselectivities were also obtained.     

Application of a C?C Bond‐Forming Conjugate Addition Reaction in Asymmetric Dearomatization of β‐Naphthols

A C C bond‐forming conjugate reaction was successfully applied to the enantioselective dearomatization of β‐naphthols. A C(sp2) C(sp3) bond is formed by using propargylic ketones as reactive partners. Good to excellent Z/E ratios and ee values were obtained by employing an in situ generated magnesium catalyst. Further transformations of the Z‐configured C C double bond in the products were achieved under mild reaction conditions. Moreover, the stereocontrolling element of this magnesium‐catalyzed dearomatization reaction was explored by computational chemistry.     

Pd‐Catalyzed Enantioselective Ring Opening/Cross‐Coupling and Cyclopropanation of Cyclobutanones

A palladium‐catalyzed enantioselective sequential ring‐opening/cross‐coupling of cyclobutanones is disclosed that provides chiral indanones bearing C3‐quaternary stereocenters. The reaction process involves palladium‐catalyzed nucleophilic addition of cyclobutanones and aryl halides, enantioselective β‐carbon elimination, and intermolecular trapping of a transient σ‐alkylpalladium complex with boronic acids. Alternatively, an intramolecular cyclopropanation is realized through C?H bond functionalization in the absence of external coupling reagents, affording chiral cyclopropane‐fused‐indanones in good yields and enantioselectivity.     

Decarbonylative Phosphorylation of Amides by Palladium and Nickel Catalysis: The Hirao Cross‐Coupling of Amide Derivatives

Considering the ubiquity of organophosphorus compounds in organic synthesis, pharmaceutical discovery agrochemical crop protection and materials chemistry, new methods for their construction hold particular significance. A conventional method for the synthesis of C−P bonds involves cross‐coupling of aryl halides and dialkyl phosphites (the Hirao reaction). We report a catalytic deamidative phosphorylation of a wide range of amides using a palladium or nickel catalyst giving aryl phosphonates in good to excellent yields. The present method tolerates a wide range of functional groups. The reaction constitutes the first example of a transition‐metal‐catalyzed generation of C−P bonds from amides. This redox‐neutral protocol can be combined with site‐selective conventional cross‐coupling for the regioselective synthesis of potential pharmacophores. Mechanistic studies suggest an oxidative addition/transmetallation pathway. In light of the importance of amides and phosphonates as synthetic intermediates, we envision that this Pd and Ni‐catalyzed C−P bond forming method will find broad application.     

Functionalized h‐BN Nanosheets as a Theranostic Platform for SERS Real‐Time Monitoring of MicroRNA and Photodynamic Therapy

Traditional therapeutic and diagnostic tools exhibit serious side effects, poor selectivity, and sensitivity. Herein, a multifunctional CuPc@HG@BN theranostic platform composed of hexagonal boron nitride nanosheets (h‐BNNS), conjugated DNA oligonucleotide, and copper(II) phthalocyanine (CuPc) was developed in which the CuPc molecule played double key roles in photodynamic therapy (PDT) as well as in situ monitoring and imaging of miR‐21 by surface‐enhanced Raman spectroscopy (SERS). Owing to the designed circle amplification of miRNA and high SERS effects of CuPc on h‐BNNS, miR‐21 responsive concentration was achieved as low as 0.7 fm in live cells. Both in vitro and in vivo data demonstrated that the integrated nanoplatform showed remarkable enhancement in PDT efficiency with minimized damage to the normal tissues. The developed probe was also successfully utilized for early monitoring and guiding the early therapy, realizing tumor elimination.     

Synthesis of Biaryls through Nickel‐Catalyzed Suzuki–Miyaura Coupling of Amides by Carbon–Nitrogen Bond Cleavage

The first Ni‐catalyzed Suzuki–Miyaura coupling of amides for the synthesis of widely occurring biaryl compounds through N?C amide bond activation is reported. The reaction tolerates a wide range of electron‐withdrawing, electron‐neutral, and electron‐donating substituents on both coupling partners. The reaction constitutes the first example of the Ni‐catalyzed generation of aryl electrophiles from bench‐stable amides with potential applications for a broad range of organometallic reactions.     

Ruthenium–Porphyrin‐Catalyzed Diastereoselective Intramolecular Alkyl Carbene Insertion into CH Bonds of Alkyl Diazomethanes Generated In Situ from N‐Tosylhydrazones

With a ruthenium–porphyrin catalyst, alkyl diazomethanes generated in situ from N‐tosylhydrazones efficiently underwent intramolecular C(sp³)? H insertion of an alkyl carbene to give substituted tetrahydrofurans and pyrrolidines in up to 99 % yield and with up to 99:1 cis selectivity. The reaction displays good tolerance of many functionalities, and the procedure is simple without the need for slow addition with a syringe pump. From a synthetic point of view, the C? H insertion of N‐tosylhydrazones can be viewed as reductive coupling between a C?O bond and a C? H bond to form a new C? C bond, since N‐tosylhydrazones can be readily prepared from carbonyl compounds. This reaction was successfully applied in a concise synthesis of (±)‐pseudoheliotridane.     

Enantioselective Synthesis of C−N Axially Chiral N‐Aryloxindoles by Asymmetric Rhodium‐Catalyzed Dual C−H Activation

The first enantioselective Satoh–Miura‐type reaction is reported. A variety of C?N axially chiral N‐aryloxindoles have been enantioselectively synthesized by an asymmetric rhodium‐catalyzed dual C?H activation reaction of N‐aryloxindoles and alkynes. High yields and enantioselectivities were obtained (up to 99 % yield and up to 99 % ee). To date, it is also the first example of the asymmetric synthesis of C?N axially chiral compounds by such a C?H activation strategy.     

Oxide‐Modified Nickel Photocatalysts for the Production of Hydrocarbons in Visible Light

Metallic nickel nanostructures that were partially decorated by discrete nickel oxide layers were fabricated by in situ reduction of calcinated Ni‐containing layered double hydroxide nanosheets, the structure of which was confirmed by extended X‐ray absorption fine structure spectroscopy, X‐ray photoelectron spectroscopy, and transmission electron microscopy. The existence of the abundant interfaces between the surface Ni oxide overlayer and metallic Ni altered the geometric/electronic structure of the Ni nanoparticles, making them apt for CO activation under light irradiation. Most importantly, the unique structure favors the C?C coupling reaction on its surface, which confers the catalyst unexpected reaction power towards higher hydrocarbons at moderate reaction conditions. This study leads to a green and sustainable approach for the photocatalytic production of highly valuable chemical fuels.     

Triphenylsilane‐fused Porphyrins

A reaction sequence of 2‐(diphenylsilyl)phenylation by Negishi coupling and intramolecular sila‐Friedel–Crafts reaction has been explored for the synthesis of mono‐triphenylsilane‐fused porphyrins 5 M and 6 M (M= Ni, Zn) and bis‐triphenylsilane‐fused porphyrins 7 M and 8 Ni . A triply linked triphenylsilane‐fused Ni^II porphyrin, 13 Ni , was synthesized in a stepwise manner involving the above reaction sequence and a final Pd‐catalyzed C?H activating arylative cyclization. The silicon atom in 13 Ni takes a distorted planarized structure with an almost perpendicular Si‐phenyl group, causing an electronic effect due to effective σ*–π* interaction.     

A SERS Optophysiological Probe for the Real‐Time Mapping and Simultaneous Determination of the Carbonate Concentration and pH Value in a Live Mouse Brain

To have a profound understanding of the physiological and pathological processes in a brain, both chemical and electrical signals need to be recorded, but this is still very challenging. Herein, micrometer‐ to nanometer‐sized SERS optophysiological probes were created to determine both the CO₃^2? concentration and the pH in live brains and neurons because both species play important roles in regulating the acid–base balance in the brain. A ratiometric SERS microarray of eight microprobes with tip sizes of 5 μm was established and used for the first time for real‐time mapping and simultaneous quantification of CO₃^2? and pH in a live brain. We found that both the CO₃^2? concentration and the pH value dramatically decreased under ischemic conditions. The present SERS technique can be combined with electrophysiology without cross‐talk to record both electrical and chemical signals in brains. To deepen our understanding of the mechanism of ischemia on the single‐cell level, a SERS nanoprobe with a tip size of 200 nm was developed for use in a single neuron.     

How and Why Does Ni0 Promote Smooth Etheric CO Bond Cleavage and CC Bond Formation? A Theoretical Study

Ni‐catalyzed cross‐coupling between aryl alkyl ethers (ArOR) and Grignard reagents (RMgBr), known since 1979, proceeds under mild conditions in many cases. Although the reaction routes of various synthetic protocols involving transition‐metal‐catalyzed C?O bond activation have been elucidated, the mechanism of this etheric Kumada–Tamao–Curriu reaction remains enigmatic. This is because oxidative addition of inert etheric C?O to Ni⁰ is thermodynamically and kinetically unfavorable, making it hard to explain the observed high reactivity of ether toward Ni catalysts. In this work, we used DFT calculations to identify a plausible reaction pathway by the Ni⁰‐ate complex, which enables smooth C?O bond cleavage and R‐group transfer with reasonable activation barriers; this mechanism also accounts for the ineffectiveness of Pd catalysts. These results throw new light on both C?O activation and cross‐coupling, and should be valuable for further rational development of the methodologies.     

Copper Catalyzed C−H Activation

Activation of C?H bonds and their application in cross coupling chemistry has received a wider interest in recent years. The conventional strategy in cross coupling reaction involves the pre‐functionalization step of coupling reactants such as organic halides, pseudo‐halides and organometallic reagents. The C?H activation facilitates a simple and straight forward approach devoid of pre‐functionalization step. This approach also addresses the environmental and economical issues involved in several chemical reactions. In this account, we have reported C?H bond activation of small organic molecules, for example, formamide C?H bond can be activated and coupled with β‐dicarbonyl or 2‐carbonyl substituted phenols under oxidative conditions to yield carbamates using inexpensive copper catalysts. Phenyl carbamates were successfully synthesized in moderate to good yields by cross dehydrogenative coupling (CDC) of phenols with formamides using copper catalysts in presence of a ligand. We have also prepared unsymmetrical urea derivatives by oxidative cross coupling of formamides with amines using copper catalysts. Synthesis of N,N‐dimethyl substituted amides, 5‐substituted‐γ‐lactams and α‐acyloxy ethers was carried out from carboxylic acids using recyclable CuO nanoparticles. Copper nanoparticles afforded N‐aryl‐γ‐amino‐γ‐lactams by oxidative coupling of aromatic amines with 2‐pyrrolidinone. Reusable transition metal HT‐derived oxide catalyst was used for the synthesis of N,N‐dimethyl substituted amides by the oxidative cross‐coupling of carboxylic acids and substituted benzaldehydes. Overview of our work in this area is summarized.     

Redox‐State‐Mediated Regulation of Cytochrome c Release in Apoptosis Revealed by Surface‐Enhanced Raman Scattering on Nickel Substrates

The interaction of cytochrome c (Cyt c) with cardiolipin (CL) is believed to play an important role in the initial events of apoptosis. Herein, we investigate the structural changes of CL‐bound Fe²⁺Cyt c and the correlation with Cyt c release through surface‐enhanced Raman spectroscopy (SERS) on nickel substrates. The SERS results together with molecular dynamics simulation reveal that Fe²⁺Cyt c undergoes autoxidation and a relatively larger conformational alteration after binding with CL, inducing higher peroxidase activity of Cyt c and higher permeability of the CL membrane compared with those induced by the Fe³⁺Cyt c. The proapoptotic activity and SERS effect of the Ni nanostructures allow the in situ study of the redox‐state‐dependent Cyt c release from isolated mitochondria, which reveals for the first time that the ferrous state of Cyt c most likely plays a more important role in triggering apoptosis.     

Cross‐Coupling of Organolithium with Ethers or Aryl Ammonium Salts by C−O or C−N Bond Cleavage

Various aryl‐, alkenyl‐, and/or alkyllithium species reacted smoothly with aryl and/or benzyl ethers with cleavage of the inert C?O bond to afford cross‐coupled products, catalyzed by commercially available [Ni(cod)₂] (cod=1,5‐cyclooctadiene) catalysts with N‐heterocyclic carbene (NHC) ligands. Furthermore, the coupling reaction between the aryllithium compounds and aryl ammonium salts proceeded under mild conditions with C?N bond cleavage in the presence of a [Pd(PPh₃)₂Cl₂] catalyst. These methods enable selective sequential functionalizations of arenes having both C?N and C?O bonds in one pot.     

Palladium‐Catalyzed Construction of Heteroatom‐Containing π‐Conjugated Systems by Intramolecular Oxidative CH/CH Coupling Reaction

Synthesis of heteroatom‐containing ladder‐type π‐conjugated molecules was successfully achieved via a palladium‐catalyzed intramolecular oxidative C?H/C?H cross‐coupling reaction. This reaction provides a variety of π‐conjugated molecules bearing heteroatoms, such as nitrogen, oxygen, phosphorus, and sulfur atoms, and a carbonyl group. The π‐conjugated molecules were synthesized efficiently, even in gram scale, and larger π‐conjugated molecules were also obtained by a double C?H/C?H cross‐coupling reaction and successive oxidative cycloaromatization.     

Reductive Cross‐Coupling Reactions between Two Electrophiles

Reductive cross‐electrophile coupling reactions have recently been developed to a versatile and sustainable synthetic tool for selective C?C bond formation. The employment of cheap and abundant electrophiles avoids the pre‐formation and handling of organometallic reagents. In situ reductive coupling is effected in the presence of a transition‐metal catalyst (Ni, Co, Pd, Fe) and a suitable metallic reductant (Mn, Zn, Mg). This Concept article assesses the current state of the art and summarizes recent protocols with various combinations of alkyl, alkenyl, allyl, and aryl reagents and highlights key mechanistic studies.     

Asymmetric Copper‐Catalyzed Carbomagnesiation of Cyclopropenes

The highly diastereo‐ and enantioselective formation of polysubstituted cyclopropanes was easily achieved through the asymmetric copper‐catalyzed carbomagnesiation reaction of nonfunctionalized cyclopropene derivatives. The carbometalated species generated in situ readily undergo C−C and C−X bond‐forming reactions with various electrophiles with complete retention of configuration.