Proton-coupled electron transfer (PCET) reactions are a kind of unconventional redox reactions, which exhibit special reactivities and selectivities due to their unique interdependent electron-proton transfer mechanisms. There are three possible pathways of PCET processes, including stepwise electron transfer followed by proton transfer (ETPT), proton transfer followed by electron transfer (PTET), and concerted pathway in which electron and proton transfer synchronously (CEPT), avoiding intermediates with high energy. These reactions have been playing a key role in numerous areas in organic chemistry, inorganic chemistry, bioorganic chemistry, organometallic and material chemistry, including the redox processes in natural and artificial systems, such as the activation for small molecules. Recently, the application of PCET reactions in organic synthesis has received a great deal of attentions and interests. Being accompanied by the development of electrochemical methods and photocatalysts, more and more novel reactions in electrochemistry and photochemistry involve PCET processes have been reported. Applying these electrochemical and photochemical methods, the activation of X—H bond has been achieved via PCET processes, including C—H bond, N—H bond, P—H bond, S—H bond or O—H bond. Thus, based on these crucial processes, a number of vital structures and fundamental frameworks can be synthesized, and various synthetic building blocks and natural products have been attained. For example, pharmaceutical building blocks like 2°-piperidines can be cyanated at their α-position; substituted dimeric pyrroloindolines such as (–)-calycanthidine, (–)-chimonanthine, and (–)-psychotriasine have also been successfully synthesized via PCET mechanism. Moreover, not only the products of reduction of multiple bonds (C=Y bond such as C=C bond, C=N bond and C=O bond), but also the products of self/cross-coupling have been achieved via PCET mechanism. In this review, the recent applications and developments of PCET mechanism in organic synthesis are summarized, including new catalyst systems and new reagents, especially with electrochemical and photochemical methodologies. The future of this area has also been demonstrated from both experimental and theoretical aspects.

Organochlorides have been widely used in medicine, pesticides, materials and other fields. In addition, organochlorides are also important synthetic building blocks. They have participated in a variety of reactions, such as free radical reactions, substitution reactions and cross-coupling reactions. The hydrochlorination of olefins is one of the most direct and efficient methods for the synthesis of organochlorides, and remakable breakthroughs have been made in the past thirty years. The research progress of olefin hydrochlorination in the past three decades is introduced. According to whether metal catalysis is involved, it is mainly classified into two categories: metal-free alkene hydrochlorination and metal-catalyzed alkene hydrochlorination. Different type of hydrochlorination reactions and related mechanisms are summarized. In addition, the future development direction of alkene hydrochlorination is prospected.

N-Heteroarenes are present in a wide variety of natural products, small-molecule drugs, organic materials, and ligands. Therefore, the methods for selective C—H functionalization of N-heteroarenes are highly sought-after for late-stage modification of pharmaceuticals. A useful tool for the synthesis of alkyl-substituted nitrogen-containing aromatic rings is the Minisci reaction, in which a protonated N-heteroarene is attacked by an alkyl radical under oxidative and acidic conditions. Classic Minisci reactions often require the use of excess oxidant, excess acid, and high temperature, which greatly limits the scope of the substrates. With the rapid development of photocatalysis in organic synthesis, in recent years, a variety of photocatalytic Minisci reactions have been reported, and successfully been applied to the synthesis of drugs. In this paper, the visible light mediated Minisci reactions in recent years are briefly reviewed.

Following the renaissances of organic electrochemistry and photochemistry, photoelectrochemical approach was arising as one of hot research areas by combination advantages of photocatalysis and electrocatalysis. The photoeletrocatalysis was widely applied in redox reactions, coupling reactions and beyond. The development of photoelectrochemical transformations during past five years is summarized and the related reactions are classified according to mechanism and catalyst. The current progresses and future outlooks of such method are also discussed.

Nitrogen-containing organic compounds are ubiquitous in natural products, drug molecules and organic intermediates. Therefore, the introduction of nitrogenous functional groups into organic compounds is of great significance. Despite transition metal-catalyzed C—N coupling reaction provided an effcient strategy to access these ntrogen-containing compounds, extra steps are generally required to obtain the pre-functionalized starting materials. Recently, transition metal-catalyzed C—H amination has emerged as a more atom- and step-economical strategy to construct C—N bonds. Compared to the noble metals (e.g. palladium and rhodium), base metal catalysts, such as copper, cobalt and nickel, have attracted dramatic attentions, due to their earth abundance, cost effectiveness, and unique catalytic activities. Herein, the recent advances in copper-, cobalt- and nickel-catalyzed C—H amination reactions assisted by directing groups were summmarized according to the types of base metals, C—H bonds, and amination reagents with an emphasis on the discussion of various amination reagents and their application. Finally, the limitations and development trend of this research field are analyzed and prospected.

Carbon dioxide (CO₂) is the main greenhouse gas, the excessive burning of fossil fuels leads to the increasing of CO₂ concentration, resulting in global warming. On the other hand, CO₂ is regarded as an ideal C₁ source due to its nontoxicity, abundance and availability. Hence, the transformation of CO₂ into fine chemicals and hydrocarbon fuels in organic synthesis is becoming one of hot research fields. Among them, the transition-metal catalyzed CO₂ hydrogenation is an appealing and promising approach for CO₂ utilization with wide potential applications, thus leading to selective fromation of 2e, 4e, and 6e reductive products including formic acid, formamide, formate, formaldehyde, methanol and C₂₊ alcohols under mild reaction conditions. In this review, the recent advances on transition metal complexe-catalyzed CO₂ hydrogenation are in detail summarized on the basis of the molecular structures, activities of the homogeneous catalysts, and product selectivity controlling. This review also gives an overview on the in situ catalytic hydrogenation corresponding to the recently developed CCU (CO₂ capture and utilization) strategy. Furthermore, the challenges and perspectives in homogeneous catalytic hydrogenation field are also given in this article.

Radical chemistry has gained its renaissence in the past decade and trendendous progresses have been witnessed in synthetic and material chemistry. However, mechanism studies are largely lagging behind comparing with rapid paces in the development of synthetic methodologies. On the other hand, the study of radical species remains a central theme in physial organic chemistry, and a large amount of thermodynamic and kinetic data on radicals have been generated over a century's reserch. Unfortuately, there has been no systematic compilation and curation of these quatitative data that are dispersedly distributed and buried in literature. As a result, most synthetic chemists are not acquainted with these valuable data. In this review, we aim in compiling and curating thermodynamic and kinetic parameters of radicals, that may hopefully provide a quantitative data basis for rational development and evolution of radical chemistry. The key parameters include radical stability energy (RSE), radical lifetime (τ), substituent constant (σ) and electrophilic index (ω). Fundamental concepts such as radical stability, Class S/O radical substitution effect, persistent/transient radical effect will be discussed on the basis of data.

Transition metal-catalyzed C—P bond activation provides an ecomomical and high-efficient route for the synthesis of organic phosphine compounds, and has received increasing attention in recent years. Owing to high bond energy of C—P bond and strong coordinative ability of P atom, the activation of C—P bond has been a fomidable challenge. Relying on substrate-preactivation and various catalysts, great progress has been achieved. This review will give a summary of this field, and according to different mechanisms of C—P bond activation and strategies of substrate pre-activation, a detailed description on reaction type, development, characteristics and mechanism will be made.

Unique reaction modes, diverse reaction sites, and structural diversity of both substrates and products have made N-heterocyclic carbene catalysis be of great of importance in the field of organic catalysis. However, there have been a lot of barriers and challenges in terms of the reactivity of substrates and the selectivity of reactions for traditional and single catalytic systems with the deep development of organic synthesis. Recently, synergistic catalysis makes it possible for previously inaccessible transformations and can adjust the reactivity and selectivity more accurately by merging two single catalytic systems, thus has emerged as a powerful catalytic strategy in organic synthesis. In this review, the latest research progress in the field of synergistic catalysis of N-heterocyclic carbenes and transition metals in the last decade is mainly reviewed.

Organophosphorus reagents play very important role in organic synthesis. The development of Wittig reaction, Staudinger reaction, Appel reaction and Mitsunobu reaction mediated by phosphine compounds is of great significance in scientific research and industrial production. In recent decades, the research on the design of P(III)/P(V) redox catalysis and catalysts to realize the catalytic mode of these reactions, and avoiding the production of stoichiometric R₃P=O has developed rapidly. This review introduces the research progress of the catalytic process of each reaction in turn. The future research direction in this field about the reactions involving stoichiometric R₃P=O is prospected.

An iridium-catalyzed intermolecular N—N coupling reaction using various N-benzoyloxyamides as acyl nitrene precursor for hydrazide synthesis has been developed. Unlike the carboxylic acid-derived dioxazolones used in previous report, this type of precursors allows the efficient synthesis of both acyl and oxycarbonyl substituted hydrazines from readily accessible precursors. Computational chemistry studies indicated that formation of the metal-acylnitrenoid intermediates via intramolecular hydrogen bond-assisted N—O cleavage may be the rate-determining step, and the subsequent nucleophilic attack of metal-acylnitrenoid by arylamines may be assisted by Cl…HN hydrogen bond to form the N—N bond.

Schisandraceae is widely spread within our country. As a kind of traditional Chinese herb, it is known for its anti-hepatitis bioactivity. The diversified and unique structures in this family have drawn the attention of many synthetic chemists. The recent efforts towards the total synthesis of schisandra triterpenoid are summarized.

Covalent organic frameworks (COFs) are a new type of crystalline porous material composed of light elements (C, O, N, B, etc.) through covalent bonds. Because of its high specific surface area, high porosity, and high crystallinity, COFs have advantages that other traditional materials can not match. By using COFs as heterogeneous ligands to support metal ions, different types of catalytic reactions can be realized, and the catalyst can be reused. The latest research progress of COFs as heterogeneous ligands supporting different metal ions to catalyze various organic reactions is summarized.

A concise strategy for the enantioselective construction of the pyridine-fused chiral bicyclo[3.3.1]nonane skeleton of (+)-huperzine A and its nanlogues was reported. The key features of this strategy are the catalytic asymmetric hydrogenation of an exocyclic γ,δ-unsaturated β-ketoester via dynamic kinetic resolution combined with an intramolecular arylation as the key steps to constuct the pyridine-fused chiral bicyclo[3.3.1]nonane skeleton. This strategy provides a concise and rapid approach to the chiral core structure of huperzine A and its nanlogues from the known starting materials (5 steps and 17.4% overall yield).

A protocol of electrochemical aziridination of electron-deficient alkenes was reported using phthalhydrazide as nitrogen source. The reaction could be conducted in undivided cell, and the ArI is essential to achieve the transformation. Hypervalent-iodine-stablized nitrene and acetyl hydroxyhydrazine were suggested as the in-situ generated nitrogen source for the stepwise aziridination. This protocol can be applied to the azirdination of α,β-unsaturated esters, amides, nitrile and ketones to give a series N-containing molecules.

Self-assembly peptide is a kind of peptide material that can form assembly under certain conditions due to the intermolecular forces such as π-π stacking and electrostatic interaction. This class of material exhibits good biocompatibility and controllability, and can form nanostructures such as granules, fibers and gels, which play a specific morphologic function and are widely used in biomedicine and other fields. In order to meet the needs of drug delivery, disease diagnosis and regulation of hydrophilic hydrophobic balance of peptides, it is necessary to perform modification for peptides. Due to the assembly characteristics of peptides and their biological functions, modified peptides have more advantages than the unmodified ones. Thus, functional modification for self-assembly peptides has been investigated intensively in recent years. The modification sites in peptide are usually the carboxyl and amino groups at both ends, as well as the active groups on the amino acid side chain. However, it is difficult for some molecules to react with peptides directly. Accordingly, two modification methods, i.e. direct and indirect modifications, have been developed in research. In this paper, the recent functionalization methods of self-assembly peptides and relevant applications are reviewed.

As the core skeleton structure of many drugs and natural products, spirooxindole derivatives have a wide range of applications in the field of biology and medicine. Efficient synthesis of spirooxindole derivatives with high enantioselectivity and diastereoselectivity has gained much attention in organic chemical community. In this paper, the asymmetric synthetic methods for C-3 five-membered spirooxindoles by catalytic intramolecular reactions, intermolecular reactions and three- component reactions are reviewed. The future development direction of this field is also prospected.

Quasi-classical molecular dynamics is a computational method that combines classical molecular dynamics and electronic structure theory, which can not only simulate the statistics of the corresponding products or intermediates in the reaction mechanism, but also provide dynamic information of chemical bond formation/cleavage on time scales. Density functional theory (DFT) calculation has been widely used in the research of reaction mechanism, but there are relatively few studies from the perspective of quasi-classical molecular dynamics, such as the phenomenon of bifurcations of transition states and their selectivity, stepwise processes appear in the concerted mechanism of cycloaddition, bypassing common intermediates and directly generating products, etc. These novel mechanism processes often require molecular dynamics, and some even break the cognition of traditional transition state theory. The recent research progress of quasi-classical molecular dynamics of organic chemical reaction mechanisms is reviewed, with emphasis on the dynamic effect in the mechanism, in order to deepening people's understanding of organic reaction mechanisms and broaden the theory of organic chemistry.

C-Nucleosides have similar structure compared to native N-nucleosides, while the carbohydrate unit and the base in a C-nucleoside are connected through a carbon-carbon bond. Because they can also be recognized and utilized by enzymes associated with N-nucleosides in cells, C-nucleosides can inhibit enzyme-catalyzed synthesis or degradation of nucleic acids, thereby inhibiting the proliferation of viruses or cancer cells. C-Nucleoside synthesis has drawn much attention since the clinical application of the C-nucleoside drug remdesivir for the treatment of COVID-19. The direct coupling of a carbohydrate moiety with a preformed aglycon unit is an efficient synthetic approach to construct aryl or heteroaryl C-nucleoside. The synthetic methods of aryl or heteroaryl C-nucleosides in recent years are summarized from three main synthetic strategies: coupling of ribose derivatives with organometallic reagents, transition metal-catalyzed coupling of ribose derivatives with organometallic reagents, and acid-catalyzed Friedel-Crafts reaction of ribose derivatives. Each synthetic strategy is categorized in terms of sugar donor precursors, including hemiacetal riboses, ribonolactones, ribofuranosyl halides, glycal, and others. The mechanism of α or β product formation in these reactions are explained in detail as well.

An one-pot reaction for the rapid construction of tricyclic fused indoline frameworks from 2-aryl indoles and N-acetyl enamides under oxygen atmosphere has been developed. The notable features of this method involve easy availability of starting materials, simple manipulation, good regio- and diastereo-selectivity, as well as environmentally friendly conditions. Mechanistic studies indicated that this reaction proceeds via oxidative dearomatization and subsequent [3+2] annulation with enamides.

A CuI-catalyzed intramolecular dearomative arylation of naphthylamines is developed through a Ullmann-type cross-coupling reaction, which led to a range of fused 3H-indole derivatives in good to excellent yields.

Under the treatment of P(NMe₂)₃, benzoylformates bearing an α,β-unsaturated ketone unit readily underwent an intramolecular cyclopropanation reaction, producing the corresponding cyclopropa[c]coumarins in moderate to good yields. Under the optimized conditions, the reaction exhibited a wide scope of substrates and excellent stereoselectivity, thus provides a facile and efficient method for the synthesis of cyclopropa[c]coumarins.

Transition-metal-nitrenoids intramolecular C—H insertion is one of the most effective methods to synthesize nitrogen-containing heterocycles. Using 2-azido-N,N-dibenzylacetamides as substrates, an iron-catalyzed intramolecular C(sp³)—H bond amination reaction under ligand-free and external oxidant-free conditions has been developed. A series of imidazolinones were synthesized in moderate to good yields.

Based on a strategy of introducing the “piperazine” bioactive group into 8-position of caffeine, sixteen novel caffeine derivatives containing substituted-piperazine moiety (Ia~Ip) have been synthesized using 8-chlorotheophylline and substituted-piperazine as materials, via multi step reactions of N-methylation, nucleophilic substitution, (protection)deprotection, etc. The structures of the title compounds were confirmed and characterized by melting point, ¹H NMR, ¹³C NMR, and HRMS. The single-crystal structure of 8-(4-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyl)piperazin- 1-yl)-1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione (Ip) was obtained. The bioassay results showed that most of the title compounds possess good insecticidal activities against Plutella xylostella L. and Mythimna separata Walker. In particular, some of the compounds exhibited better larvicidal effect towards Plutella xylostella L. than that of control caffeine, among which 8-(4-(4-fluorophenyl)piperazin-1-yl)-1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione (Ie) and 1,3,7-trimethyl-8-(4-(4- nitrobenzoyl)piperazin-1-yl)-3,7-dihydro-1H-purine-2,6-dione (In) at a test concentration of 100 mg•L^–1 held lethality rate of 60% and 53%, respectively. In addition, partial compounds at 50 mg•L^–1 concentration possessed >50% fungicidal activities against Physalospora piricola, Rhizoctonia cerealis, Sclerotinia sclerotiorum, etc. The research results in this paper provide useful reference for further design of novel agrochemicals based on the natural product structure of xanthine.

An organocatalyzed asymmetric formal [4+2] annulation of ortho-hydroxyl functionalized p-quinone methides with β-keto acylpyrazoles has been developed, which provides an efficient approach to access optically active 3,4-dihydro- coumarins. Under the catalysis of a quinine-derived bifunctional squramide, the reactions of a wide range of ortho-hydroxy- phenyl substituted p-quinone methides and β-keto acylpyrazoles took place smoothly to generate the corresponding polysubstituted 3,4-dihydrocoumarins in good yields with high levels of diastereo- and enantio-selectivities (up to 96% yield, >19/1 dr and 98% ee) under mild reaction conditions.

The synthesis and structure of 4'-CF₃-uridine modified ribonucleotides are reported. Active 4'-CF₃-uridine (^4'-TfMU) phosphoramidite was prepared and successfully incorporated into oligonucleotides based on solid-supported synthesis. Molecular dynamics simulations and NMR studies of the ^4'-TfMU modified oligonucleotides revealed that the ribose of ^4'-TfMU was constrained in the South conformation, which was corroborated by the biochemical properties of the ^4'-TfMU modified oligonucleotide, such as their affinity to complementary strands and transesterification kinetics. The South-constrained conformation, together with the intense ¹⁹F NMR signal of the ^4'-TfMU makes it an ideal probe for studying the structure and function of RNA.