Molnupiravir is an oral drug against SARS-CoV-2 infection approved by Britain and America in 2021. Currently, the reported synthetic methods of molnupiravir have disadvantages, such as long steps, limited yield and high cost. Efficient methods for the synthesis of molnupirovir through direct acylation of low-price cytidine are developed. In different proportions of aqueous tetrahydrofuran solution, selective isobutyrylation of hydroxyl of cytidine and further 2',3'-deprotection of 2',3',5'-tri-O-isobutyrylcytidine could be realized, which successfully gave 5'-O-isobutyrylcytidine. Finally, N⁴-hydroxylation of 5'-O-isobutyrylcytidine yielded molnupirovir. Using this straightforward and high-yielding three-step approach, molnupirovir was obtained from cytidine in 82% overall yield.

Most of the traditional organic fluorescent molecules have notorious aggregation-induced quenching (ACQ) effect, which limits their application in many fields. Therefore, how to achieve the transition from ACQ to aggregation-induced emission (AIE) while maintaining the functional properties of traditional conjugated molecules is of great significance. In recent years, many research groups have done a lot of breakthrough works in this field. According to the construction method and structural characteristics of AIE luminogen (AIEgen), the ACQ to AIE transformation strategy can be divided into two types. Based on the restriction of intramolecular motion (RIM) mechanism, the first one is to decorate ACQphore with typical AIEgen (e.g. tetraphenylethene unit). As the second one, some functional units (e.g. triphenylamine and cyanoethylene moiety) are introduced to realize the construction of AIE molecules from zero starting point as the RIM mechanism. In the latter, the construction of other AIEgen systems involving isomerism and excited-state intramolecular proton transfer (ESIPT) mechanisms has also been prominent recently. Thus, according to these classifications, the new progress on the construction strategy of ACQ-to-AIE transformation in the past five years is summarized from the four aspects of AIEgens’ structure, performance, mechanism and application.

Chiral tertiary alcohol is widely present in a series of bioactive compounds, natural products and pharmaceuticals. Consequently, the development of efficient asymmetric catalytic methods for their syntheses is highly important. Kinetic resolution (KR) is an important strategy to access enantioenriched alcohols from racemic alcohols. However, due to the requirement to distinguish three none-hydrogen substituents at the α-position of tertiary alcohols, it is challenging to develop highly efficient kinetic resolution protocols for tertiary alcohols with broad substrate scope. Nevertheless, significant progress has been made in the field of nonenzymatic kinetic resolution of tertiary alcohols in recent years, and a number of novel asymmetric reactions and catalytic systems have been successfully applied in the KR of tertiary alcohols. The tremendous advances in the kinetic resolution of tertiary alcohols are comprehensively reviewed, the substrate scope, characteristics, mechanisms and limitations of these methods are summarized, and our perspective on this research field is also provided.

Starting from commercially available simple olefins, alkene isomerization could realize the efficient construction of multi-substituted alkenes, which might be difficult to access with other synthetic methods, in an atom-economic manner via the stereoselective or positional-selective modulation of the carbon-carbon double bonds. The palladium catalyzed stereoselective (Z/E) and the positional selective isomerization reactions of alkenes are summarized. The mechanistic perspectives, and their synthetic applications in the synthesis of drug molecules and natural products are discussed in detail.

Coupling reagents mediate the formation of amide bonds and play a key role in solid phase peptide synthesis. The novel N,N-diisopropylcarbodiimide (DIC)/ethyl cyanoglyoxylate-2-oxime (Oxyma) condensation system has the advantages of low cost, operational safety, higher coupling efficiency and lower rate of racemization. The DIC/Oxyma condensation system has been widely used in manual and automated synthesis of peptides. However, the ideal reaction ratio in DIC/Oxyma condensation system at mild reaction temperature remains to be further investigated. GsMTx4 is a cysteine rich peptide toxin identified from the venom of Grammostola spatulata spider, which consists of 34 amino acid residues and three pairs of disulfide bonds. GsMTx4 is the only inhibitor specifically targeting piezo channel, which is a multifunctional mechanically sensitive cation channel and associated with a variety of hereditary diseases. Herein, the synthetic efficiencies of different reaction ratios of DIC and Oxyma at moderate reaction temperature were systematically evaluated. The efficiency and robustness of DIC/Oxyma condensation system were validated by the rapid manual synthesis of linear GsMTx4. The one-step oxidative folding strategy was applied for the construction of three pairs of disulfide bridges, affording the active GsMTx4. The circular dichroism and patch-clamp electrophysiology tests were conducted to evaluate the structure and activity of synthetic GsMTx4. In summary, a fast, robust and safe synthetic method based on DIC/Oxyma is established, which is particularly useful for the manual synthesis of peptides.

Copper-catalyzed Chan-Lam reaction represents an important and highly efficient method for the synthesis of organic molecules containing carbon-heteroatom (C—N, C—O, C—S) bonds, which has many advantages such as mild conditions, wide substrates range and high yields. Therefore, the Chan-Lam coupling reactions are extensively applied in organic synthesis, medicinal chemistry and material science, etc. Although many catalytic systems using different copper salt alone or in combination with various ligands for Chan-Lam coupling reaction have been extensively reported by different groups, the studies on the Chan-Lam coupling reaction employing well-defined copper complexes as catalysts were underdeveloped. In recent years, the Chan-Lam reactions catalyzed by copper complexes with different ligands have attracted more special attention from synthetic chemist and made many achievements. Some novel copper complexes have been designed and synthesized, which were further used as efficient catalysts for Chan-Lam coupling reactions of arylboronic acids with various nucleophiles. The recent progresses on Chan-Lam coupling reactions catalyzed by well-defined copper(II) complexes are summarized from two aspects of homogeneous catalysis and heterogeneous catalysis in detail. Then the homogeneous Chan-Lam reactions are classified by the different coordination mode of copper complexes, and the heterogeneous Chan-Lam reactions are described according to chronological order. The reaction mechanism on Chan-Lam coupling proposed by different research groups is also straightened out and discussed. Finally, the development prospects of this research field are pointed out.

The absolute configuration (AC) assignment of chiral molecules is crucial to the research and application of chiral chemistry. In recent years, various methods for the AC determination for chiral compound fall mainly into three categories according to their principles. The first is the nuclear magnetic resonance (NMR)-based method for determining the AC of chiral compound by exciting the nucleus of the chiral compound in the chiral environment, including the NMR-based method using aromatic ring diamagnetic shielding effect and the NMR method using sugar shift effect. The second is X-ray diffraction (XRD) methods based on atomic resonance scattering, including single crystal and powder XRD. The third is based on the enantiomer refraction and absorption of polarized light, including optical rotation spectroscopy, electronic circular dichroism, vibration circular dichroism and vibration Raman spectroscopy. In addition, other methods such as enzyme-based and homobenzotetramisole (HBTM)-based methods are supplementary. Based on our research experiences in chiral fluorescent recognition and chiral drugs, the principles and application of these methods, aiming to afford beneficial references for chiral chemists and related workers are reviewed.

In recent years, vinyl radical-mediated hydrogen atom transfer (HAT) has received increasing attention. This protocol provides an efficient pathway for radical cyclization and regioselective C(sp³)—H bond functionalization including vinylation, alkynylation, halogenation, arylation, etc. Generally, vinyl radicals are generated from single electron reduction of vinyl halides or the addition of extra radical to alkynes. The reaction pathways depend on substrates. For example, the resulting alkyl radical arising from vinyl radical-mediated HAT process is prone to be intramolecularly re-added to alkene, leading to cyclic products. When employing specific propargyl alcohols as substrates, the cyclic alkyl radical intermediate undergoes β-scission of C—C bond to realize vinyl migration. In addition, intermolecular radical trapping usually occurs by using internal alkynes. The transformation based on vinyl radical-mediated HAT features high regioselectivity, good atom-economy, and broad diversity of reaction modes. The recent advances in this research area are summarized.

Boron dipyrromethene (BODIPY) dyes are widely used in the fields of life sciences, chemical analysis and optoelectronic materials due to its excellent photophysical properties, favorable biocompatibility, facile synthesis and modification etc. The synthesis and derivative strategies of BODIPY provide the basis for its wide application and have attracted great attention from researchers. In this review, the modification strategies for different reaction positions of BODIPY have been discussed, and Pd-catalyzed cross-coupling reactions and oxidative coupling reactions about BODIPY are discussed individually. Finallly, the development of this field is prospected.

The photo-transition metal synergistically catalyzed coupling reaction provides a new research strategy for the development of metal-catalyzed coupling reactions. In this catalytic system, the excited state photosensitizer controls the valence state of the transition metal intermediate through a single electron transfer process, there by regulating the coupling reaction process, especially for the process that is difficult to occur in traditional transition metal catalysis. In addition, the excited photosensitizers could also promote the coupling reaction through the energy transfer process. Simultaneously, the light-promoted transition metal-catalyzed C—X bond coupling reactions without external photosensitizers have also been rapidly developed. Light and transition metals synergistically catalyzed coupling reactions provide an important tool for the construction of C-heteroatom bonds, showcasing broad application prospects in synthetic chemistry.

Over the past few decades, transition metal-catalyzed reactions have been developed into a powerful tool for building various chemical bonds. At the same time, non-metal-promoted chemical bond construction reactions have attracted more and more attention of synthetic chemists because of the avoiding of using expensive metal catalysts and ligands, resulting in the reduce of reaction costs and environmental pollution. It conforms to the concept of green chemistry development. Among them, potassium tert-butoxide-promoted cyclization and coupling reactions have been rapidly developed. The intramolecular cyclization and intermolecular coupling reactions involving potassium tert-butoxide since 2000 are summarized, and the possible reaction mechanisms are elucidated, which can help chemists better understand the development of this field and promote the development of this field.

Proteins are the most abundant biomolecules in nature and are involved almost in all living processes. Chemical modification of proteins is an efficient strategy to mediate and study the physical and chemical properties and biological functionalities of proteins. Most protein chemical modifications are based on the bioorthogonal reactivities of the side chain functional groups of certain amino acid residues. Among 20 proteinogenic amino acids, cysteine has become the best choice for chemical protein modification, owning to its relative low abundance in proteins, the unique nucleophilicity and low redox potential of its mercaptan group. The recent advances in chemical protein modification via cysteine are comprehensively reviewed and the challenges and applications for future development are discussed.

Sulfoximines represent an important structural motif in organic chemistry, and have been utilized as chiral auxiliaries, chiral ligands and organocatalysts. They also serve as key intermediates for the construction of heterocyclic compounds. Attributing to their unique bioactivities, sulfoximines have been developed as previliged pharmacophores and widely used in pharmaceutical chemistry and agriculture. Considering the wide applications, the synthetic methods to afford sulfoximines have attracted increasing attention. Among them, the direct arylation of NH-sulfoximines to prepare NAr- sulfoxmines exhibites some unique advantages, including atom-economics, mild conditions and step-economics, and thus has made tremedous progress in recent years. Various methods of NH-sulfoximines to afford NAr-sulfoximines via a C—N bond formation strategy, as well as their applications in synthesis of bioactive molecules and ligands for transition-metal catalysts, are reviewed.

The seven-membered rings represent an important structural motif and have found wide presence in natural products, biologically active molecules and drugs. In contrast to the five- and six-membered rings, the construction of seven- membered ring remains challenging. Thus, the developing efficient strategies for the synthesis of seven-membered rings is very desirable. N-Heterocyclic carbene (NHC) organocatalysis has been recognized as a powerful and unique tool for the quick construction of complex molecular architectures. Nevertheless, whereas significant advances have been made using NHC as catalysis. However, most of these works concentrated on the assembly of five or six-membered rings. This review highlights the developments and new advances for the construction of seven-membered rings catalyzed by NHC. The aim of this review is to provide an overview of this area and inspire synthetic chemists to develop more efficient and novel strategies for the construction of seven-membered rings.

The synthesis of oxygen-substituted N-hydroxy phthalimide derivatives is essential due to their ubiquity in natural products and pharmaceuticals. Metals or peroxides are often required for most C=C/C—H bond activation methods used for olefins, ketones, esters, aldehydes and alcohols. Using cheap and safe iodobenzene diacetate as a feasible dehydrogenation agent and N-hydroxy phthalimide as free radical precursor, the dioxidation of olefins, α-oxidation of carbonyl compounds, oxidation of aldehydes, and oxidative esterification of primary alcohols were successfully realized. This method occurs via a radical mechanism and has the characteristics of mild metal-free reaction conditions, good compatibility and wide substrate scope.

α-Chiral primary amine subunits are widespread structural units in a large number of pharmaceutical molecules and are key intermediates toward the preparation of numerous amine-containing drugs. Versatile functionalizations on the NH₂ group also supply a quick way to construct molecular complexity. Additionally, chiral primary amines can serve as ligands or organocatalysts which can be applied in organic synthesis. Therefore, efficient synthetic routes toward chiral primary amines have attracted tremendous attention. Asymmetric chemo-catalytic reactions that are capable of directly preparing chiral primary amines remain scarce. Transition-metal-catalyzed asymmetric reductive amination (ARA), a reaction type that transforms easily available ketones and amines into chiral amines in the presence of a chiral metal-catalyst and reductant, is among the most straightforward methods to access chiral amines. However, studies on ARA are still limited compared to that on imine hydrogenation, probably due to the presence of competitive ketone reduction as the side reaction. ARA using ammonium salts as the amine sources can directly yield chiral primary amines from prochiral ketones and are thus highly attractive and of great significance. In addition to competition with ketone reduction process, this reaction also faces some other challenges, including: (1) NH₃ or the produced primary amines can coordinate to the metal center which results in catalyst poisoning effect; (2) the coordination of amine ligand to the metal center may lead to ligand exchange that enhances the challenge on asymmetric control; (3) the produced primary amines may undergo further alkylation process via double reductive amination, thus providing more complicated outcome. The existing problems and challenges in ARA require urgent development of applicable catalytic systems. Aiming to solve some challenges in the field of ARA with ammonium salts, we have carried out systematic studies and will present the latest progress achieved from our team in this account.

The N-deacylation of amides under mild conditions is highly desirable in organic synthesis, but it remains challenging due to the chemically robust nature of amide bond. A general solution to the N-deacylation of amides with NH₃•H₂O under mild and scalable conditions (10 mmol) was developed. A range of drugs and drug derivatives including indomethacin, N-acetyl melatonin and N-acetyl carprofen could be deacylated to release free amines in excellent yields. The good functional group compatibility, combined with operational simplicity, excellent yield and cost effectiveness of all reagents, makes this protocol a prime candidate for N-deacylation of amide.

Organosilanes have been widely applied in synthetic chemistry, materials, pharmaceuticals, agrochemicals due to the special properties. The synthesis of organosilanes has been successfully developed by several strategies including nucleophilic substitution, hydrosilylation of alkene and C—H silylation. In recent years, significant achievements have been advanced in the cross-coupling of C—Si bond by using of silyl electrophiles, especially in the break-through of the reductive cross-coupling of silyl electrophiles and carbon electrophiles. It is emerging as one of the hottest issues in synthetic chemistry. In the review, the recent progress on the cross-coupling for C—Si bond formation by using of silyl electrophiles is summarized. The reaction type including silyl-Heck, silyl-Negishi, silyl-Kumada, silyl-reductive-electrophile-coupling, multicomponent coupling reaction and radical silylation was mainly discussed. In the meanwhile, the intramolecular C—Si coupling via demethylation of aryl silanes is also discussed.

Amino acids are an important class of biomass raw materials, which are widely used as starting materials to synthetize bioactive molecules, drugs and functional materials, and are also useful as organic catalysts or metal ligands for asymmetric synthesis. Visible-light-induced organic transformation has attracted enormous interest due to its intrinsic characteristics of sustainability and green chemistry. The use of visible-light to promote decarboxylative coupling of α-amino acids to construct various nitrogen-containing compounds has been considered as an attractive synthetic strategy. This review highlights the recent progress in photocatalytic decarboxylative coupling reactions of α-amino acid derivatives with various partners.

Benzylated quinones widely exist in natural products and drug molecules. Thus their convenient synthesis with high efficiency brings great significance. However, hard conditions are still essential among the present reports. Herein, the development of visible light-induced metal-free benzylation of quinones via cross dehydrogenation coupling reaction with methylene blue as photocatalyst, tert-butyl hydroperoxide as oxidant, and toluene derivatives as benzylation reagent is reported. The reaction exhibits many advantages, including mild conditions, a broad scope with good functional group tolerance, low cost, and avoidance of metal remaining in products. This method may bring novel inspiration and approach for synthesis of bioactive quinones.

As an important kind of synthons, thiosulfonates can react with alkynes, alkenes, aldehydes, and halogenated hydrocarbons to synthesize thioethers and sulfones. At the same time, some thiosulfonate compounds have anti-viral and anti-fungal bioactivities. The synthesis of thiosulfonates and their applications in organic synthesis have been under the spotlight. Thus, according to different types of catalysts and new progress in green chemistry, the synthesis progress of thiosulfonates is summarized. On the other hand, according to the types of reactants and reaction types, the application progress of thiosulfonates in organic synthesis is reviewed. In the future, among the researches on the construction of new sulfides with thiosulfonates, various difunctionalization reactions are still promising directions.

A chiral phosphoric acid catalyzed aza-1,8-conjugate addition of isoxazol-5(4H)-ones to 6-methylene-6H-indoles formed in situ from 6-indolylmethanols has been developed for the first time. Notably, the remote stereocontrolled 1,8-addition of isoxazol-5(4H)-ones was featured by N-selectivity, affording aza-adducts in 70%~83% yields with 61%~96% ee.

Toluene derivatives are alkyl aromatic hydrocarbons derived from oil and natural gas and are among the cheapest and most readily available materials for the chemical industry. C—H functionalization is important for the synthesis of various bioactive substances, and inert benzylic hydrocarbon bond activation has long been a big challenge in this field due to the high hydrocarbon bond energy. Therefore, the development of simple and efficient methods for C—C and C—X bonds formation has been demonstrated as one of the hot topics by activating the benzylic C(sp³)—H bonds in recent years. The progress in benzylic C(sp³)—H functionalization of toluene and its derivatives under different catalytic conditions in the past decade is summarized according to different reaction classifications. The reaction substrate compatibility, mechanism, applications, advantages and limitations in this field are also discussed in detail.

Nitrogen-nitrogen bonds are widely found in drugs, nature products and organic materials. Design and synthesis of nitrogen-nitrogen motifs with high efficiency have always been an important issue in organic chemistry. The nitrogen sources such as amines, nitriles, nitroso, and azides or other N-functionalized reagents, are commonly exist in organic compounds. Direct N-N coupling of these nitrogen sources provides a more convergent synthesis strategy to produce different heterocycles and hydrazines containing the N-N motif. In this paper, the intermolecular and intramolecular formation of N—N bond in recent years is reviewed, and the difficulties and future development of this method are prospected.

Chirality is widely found in many natural products and drug molecules. It is of great significance to obtain optically pure chiral compounds because of the fact that different enantiomers have distinct or even opposite physiological activities. Deracemization is the most direct, efficient and atom-economic approach to obtain a single enantiomer, and the emerging photocatalytic deracemization attracts much attention because of its high efficiency. Herein, the recent advances in photocatalytic deracemization are summarized. The future research direction of this field is also prospected.

The discovery of aggregation-induced emission (AIE) has created a new milestone and new situation in the research of organic luminescence materials. The research on AIE molecules has attracted enormous attention. Among them, trisubstituted olefinic AIE molecules, as new structural types in recent years, have made remarkable progress in their design, synthesis and application. In view of this, according to the structural characteristics of the substituents attached to the carbon-carbon double bond, these trisubstituted olefinic AIE molecules synthesized in recent years are divided into three categories: olefinic AIE molecules substituted (a) by multiple aryl rings, (b) by cyano group(s) and (c) by heteroatoms. As this classification, their molecular mechanisms and applications in the field of organic luminescence materials and fluorescent probes are reviewed, and the future design of the trisubstituted AIE molecules is also prospected.

Sulfur-containing heterocyclic compounds are widely applied in many areas such as drugs, molecular devices and materials, etc., so their synthesis methods have attracted much attention. The key step for the synthesis of sulfur-containing heterocycles is the construction of C—S bond, which is generally realized by C—H bond functionalization or C—X bond coupling reaction with sulfur-containing organic or inorganic substances. Elemental sulfur is cheap, available and stable, and it is an excellent sulfur atom donor for the synthesis of sulfur-containing heterocycles. Therefore, the synthesis of sulfur-containing heterocycles from elemental sulfur has become a research hotspot. Herein, the recent research progress of synthesis of sulfur-containing heterocyclic employing sulfur as sulfur-source is reviewed.

As a class of small organic molecules containing (NC) functional groups with high activity, isocyanide has been widely employed in organic synthesis, materials science, as well as coordination chemistry. In recent years, the transition metal-catalyzed isocyanide insertion reactions have attracted much attention due to the convenient and simple operations, the efficiency in the formation of diverse new bonds and good reaction selectivity. A series of highly useful chain or cyclic compounds have been successfully constructed using this strategy, such as functionalized ketones, amides, nitrogen heterocyclic compounds, etc. To study the most recent progress, the advances in transition metal-catalyzed isocyanide insertion reactions since 2017 to 2021 are briefly summarized according to different metal categories, and the future development has also been prospected in this review.

The biological importance of quinoxalin-2(1H)-ones has inspired increasing pursuit for the development of efficient and expedient synthetic methods to access these entities. Among them, C3—H functionalization of quinoxalin-2(1H)- ones has been a sought-after strategy in recent years, especially using photocatalysis platform to trigger radical intermediates. Besides the direct addition of photocatalysis-yielding radicals to 3-position of quinoxalin-2(1H)-ones, a handful of three- component cascade reactions have been described, wherein olefins were used to preferentially accept radicals to generate new radical intermediates to experience the second addition process. Given the robust ability of cascade strategy to enrich the varieties of quinoxalin-2(1H)-ones, the exploration of new protocols remains a highly attractive task. Herein, we report photoredox catalytic reactions of quinoxalin-2(1H)-ones with 2-bromo-1-arylethan-1-ones as the partners, leading to a series of valuable 1,4-diketone-functionalized quinoxalin-2(1H)-one derivatives with satisfactory results. This is an unprecedented cascade reaction strategy, involving radical addition to quinoxalin-2(1H)-ones and the resultant intermediates to accept a second addition of radicals generated from bromide substrates or to experience S_N2 reaction with bromides.

Organosilicon compounds containing C(sp³)—Si bonds are widely used in many research fields, such as material science, pharmaceutical chemistry and fine chemical synthesis. In recent years, due to its high atomic economy and step economy properties, the direct catalytic silylation of C(sp³)—H bonds to form C(sp³)—Si bonds has become one of the research hotspots in the syntheis of new organosilicones containing C(sp³)—Si bonds. The research progress of direct catalytic silylation of C(sp³)—H bonds is summarized in detail, and the mechanism and application range of related silylation reactions are also discussed.

Seven-membered ring skeletons widely exist in many natural products and drug molecules, and it is of great significance to develop efficient asymmetric synthesis methods for seven-membered ring compounds. The progress in the asymmetric synthesis of seven-membered ring compounds by transition metal-catalyzed cycloaddition reactions since 2000 is reviewed. The future development direction of this field is also prospected.

Organophosphine-catalyzed cycloaddition reaction provides an efficient method for the construction of valuable heterocycles. In this article, density functional theory calculations were performed on the mechanism of a phosphine-catalyzed [4+2] cycloaddition between conjugated dienes and enones reported recently. The overall reaction consisted of four sequential processes, namely the formation of the zwitterionic intermediate, intermolecular nucleophilic addition, intramolecular cyclization, and removal of the organophosphine. The activation free-energy barrier was estimated to be 84.4 kJ/mol, and the overall free-energy change was computed to be –18.8 kJ/mol. For the asymmetric variant of the reaction, the predicted enantioselectivity results were consistent with experimental findings, and what’s more, a distortional strain model was proposed to understand the observed enantioselectivity. Lastly, the substituent effects concerning the diene substrate were explored, which revealed that an ester group on the C(2) position would exert a much stronger influent on the reactivity than that on the C(1) position. The conclusions drawn in this work can help organic chemists to optimize experimental conditions and design new reactions.

Catalytic nitrene transformations to N-containing molecules through direct C—N bond formation have experienced a dramatic development in the last decades. Although a variety of nitrene precursors have been disclosed under the corresponding catalytic conditions, which play a principal role in the synthesis of nitrogen-containing molecules with structural complexity, the types of nitrene transfer reactions mainly limited to the amination, aziridination, sulfimidation, and few others. In this area, reviews focused on different nitrene precursors, catalytic strategy (or metal catalysts), and challenging synthesis have been well-documented. In this review, the catalytic approaches of nitrene addition with alkynes, mainly nitrene/alkyne metathesis cascade reactions are outlined, which provide expeditious access to polycyclic, fused, and spiro N-heterocycles with structural diversity.

Fluoro-containing heterocyclics play an important role in many fields, such as organic chemistry, pharmaceutical chemistry and material science due to their excellent physical and chemical properties. However, there are few natural fluoro-containing heterocyclics in nature, so it is particularly important to develop efficient synthesis methods of fluoro- containing heterocyclics. With the rapid development of transition metal catalyzed, photocatalyzed and electrocatalyzed radical reactions, radical chemistry has made a breakthrough in the field of synthesis and stimulated the interest of organic chemists in constructing fluoro-containing heterocyclics by using radical chemistry. In this paper, monofluoroalkylation, difluoroalkylation, trifluoromethylation, trifluoroalkoxy/sulfur/selenylation, perfluoroalkylation of unsaturated hydrocarbons and direct C—H fluoroalkylation of heterocycles are classified, and the construction of fluorine-containing side chain heterocycles mediated by free radicals is discussed from the aspects of transition metal catalysis, photocatalysis and electrocatalysis.

2-Pyrone is a type of heterocycles with a conjugated diene motif. It can react as a privileged diene in Diels-Alder reactions. In the past several decades, 2-pyrone-based Diels-Alder reactions have been widely used in the total synthesis of complex natural products. Therefore, the catalytic asymmetric Diels-Alder reactions of 2-pyrones have attracted increasing attention from the synthetic community in recent years. The research progress of catalytic asymmetric normal-electron-demand Diels-Alder reactions and inverse-electron-demand Diels-Alder reactions, and their applications in total synthesis of natural products are summarized.

The AsPh₃/iridium catalyzed diborylation of unactivated primary C(sp³)—H bonds using pyrazoles as directing groups was disclosed. This method could tolerate a variety of functional groups, affording a vast array of 1,1-diboron alkanes in moderate to good yields. The synthetic utility of the current method on a gram-scale reaction for further functionalization was also demonstrated.

Diazo compounds have rich reactivity and are important synthetic intermediates in organic synthesis. Diazo compounds are commonly used as the precursors of transition metal carbenes, and the relative transition metal catalyzed reactions have achieved many important progresses in the past decades. In sharp contrast, radical reactions with diazo compounds as a key component are still less explored. Owing to the easy generation of diverse radical intermediates under mild conditions, visible-light photoredox catalysis has emerged as a powerful tool for organic synthesis. By the combination of visible light photoredox catalysis and diazo compounds, some novel reactions that different from the classical carbene processes have been developed, which further extend the synthetic applications of these reagents. The progresses of radical reactions of diazo compounds enabled by visible light photoredox catalysis in the past five years are summarized, including: (1) diazo compounds as the nucluophiles, (2) diazo compounds as the equivalents of carbyne precursors, (3) diazo compounds as the radical acceptors, and (4) diazo compounds as the radical precursors. We wish that the detailed discussion on the mechanism of the reactions would help the audiences to understand the features of radical reactions of diazo compounds and the realative visible light chemistry.

Propargyl alcohols as a classical bifunctional group compounds possess alcohol hydroxyl group and carbon-carbon triple bond. Due to their special structure, they show unique reaction characteristics, and are employed in reactions via activating its alcoholic hydroxyl group or triple bond. The most typical reaction for propargyl alcohols is various cyclization reactions with different compounds to assemble a richer variety of cyclized compounds such as cyclopentene, pyrrole, furan, cyclic carbonate, pyran, pyridine and azepine cyclic compounds. The recent research progress in the cyclization reaction of propargyl alcohols with various compounds, including [3+2], [2+3], [3+3], [4+2], [2+4], [4+1], [3+4] and other types of cyclization reactions, is summarized.

Quinones and their imine counterparts constitute a class of highly electrophilic and dearomatized synthon. Their preparation and synthetic applications are challenged by limited stability due to the tendency of dimerization/polymerization and hydrolysis. By taking a biomimetic catalytic oxidation strategy, we have developed oxidation systems comprising metal catalysts and green terminal oxidants that realized in situ oxidation of phenols and reactivity modulation of labile quinone intermediates. This has led to the establishment of several [3+2], [3+3] and [4+2] cycloadditions and control of their regioselectivity and stereoselectivity. In this account, our recent advances in reactivity modulation of labile quinones/quinone imines and their biomimetic catalytic transformations are summarized.