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We report a general, scalable, and convenient photochemical process for diversities of distal oxygenated nitriles from corresponding less-strained ketoxime esters allowing one-step introductions of ether and cyano groups, which avoids the utilization of toxic cyanide reagents. A wide range of ketoxime esters involving five-membered to eight-membered cycloketoxime esters and linear ketoxime esters participate smoothly under operately simple and mild conditions, affording structurally variable ring-opening products.

Enantioenriched phosphorus compounds play crucial roles in many fields ranging from catalyst to materials science to drug development. Despite advances in the construction of phosphacycles, incorporation of a P-chirogenic center into heterocycles remains challenging. Here, we report an effective method for the preparation of phosphacycles through nickel-catalyzed [4+2] heteroannulation of internal alkynes with aminophosphanes derived from o -haloanilines. Notably, chiral 2-λ5-phosphaquinolines can be prepared from P-stereogenic substrates via NH/PH tautomeric equilibrium without loss of stereochemical integrity. The strategy is found to exhibit a broad scope in terms of both reaction components, enabling modular construction of libraries of 2-λ5-phosphaquinolines with different steric and electronic properties for fine-tuning photophysical properties, where some of these compounds showed distinct fluorescence with high quantum yields. A series of mechanistic studies further shed light on the pathway of the heteroannulation and reasons for stereospecificity.

Hemilabile ligands have been applied extensively in transition metal catalysis, but preparations of these molecules typically require multistep synthesis. Here, modular assembly of diverse phosphine-amide ligands, including related axially chiral compounds, is first reported through ruthenium-catalyzed C-H activation of phosphines with isocyanate directed by phosphorus(III) atoms. High reactivity and regioselectivity can be obtained by using a Ru3(CO)12 catalyst with an MPAA ligand. This transformation significantly expands the pool of phosphine-amide ligands, some of which have shown excellent efficiency for asymmetric catalysis. More broadly, the discovery constitutes a proof of principle for facile construction of hemilabile ligands directly from the parent monodentate phosphines by C-H activation with ideal atom, step and redox economy. Several dinuclear ruthenium complexes were characterized by single-crystal X-ray diffraction analysis revealing the key mechanistic features of this transformation.

Summary Heteroarenes containing oxygen, nitrogen, and/or sulfur are important in numerous aspects of chemistry and everyday life. C–H functionalization of heteroarenes represents the fastest and most atom-economical approach for the synthesis of complex molecules. This strategy avoids the requirement of de novo synthesis and is beneficial for the late-stage modification of structurally complex molecules. Although early protocols for C–H functionalization using organic halides (I, Br, and Cl) as coupling partners remain in active use today, a range of modern strategies allows the cleavage of less reactive C–Het (F, O, S, N, and P) and C–C bonds to form essential links to the feedstock chemicals, highlighting their renewable and sustainable features. This review focuses on modern strategies for the C–H functionalization of heteroarenes with these alternative coupling partners. Most of the transformations can be achieved through catalytic processes. Some non-catalytic strategies involving new reagents and techniques are also introduced.

Alkyl constitutes one of the most widely used groups in organic synthesis. Here, the development of a series of thianthrenium salts, which act as reliable alkylation reagents, are ready to engage in copper-catalyzed Sonogashira reaction to build C(sp 3 )-C(sp) bonds under mild photoinduced conditions. Diverse alkyl thianthrenium salts, methyl and disubstituted thianthrenium salts are employed with great functional breadth, since sensitive Cl, Br and I are compatible and challenging to achieve by conventional approaches. The generality of the developed alkyl reagents has also been demonstrated in copper-catalyzed Kumada reactions.

An efficient method for the synthesis of deuterated homologation of boronate esters was developed. This discovery uses robust deuterated agent 5-(methyl-d3)-5H-dibenzo[b,d]thiophen-5-ium trifluoromethane sulfonate (DMTT) as d2-methylene source. Mechanistically, base promoted deprotonation of DMTT to generate d2-sulfur-methylene ylide intermediate, which attack the boron atom of boronic ester and followed by 1,2-migration to afford the deuterated boronic homologues. The developed protocol provides a unique approach to achieve one-carbon growth under the practical mild conditions.

Robust strategies to enable the rapid construction of complex organoboronates in selective, practical, low-cost, and environmentally friendly modes remain conspicuously underdeveloped. Here, we develop a general strategy for the site-selective C-H borylation of pyrroles by using only BBr 3 directed by pivaloyl groups, avoiding the use of any metal. The site-selectivity is generally dominated by chelation and electronic effects, thus forming diverse C2-borylated pyrroles against the steric effect. The formed products can readily engage in downstream transformations, enabling a step-economic process to access drugs such as Lipitor. DFT calculations (𝑤B97X-D) demonstrate the preferred positional selectivity of this reaction.

The use of an operationally convenient and stable silicon reagent (octamethyl-1,4-dioxacyclohexasilane, ODCS) for the selective silacyclization of (hetero)arenes via twofold C-H activation is reported. This method is compatible with N-containing heteroarenes such as indoles and carbazoles of varying complexity. The ODCS reagent can also be utilized for silacyclization of other types of substrates including tertiary phosphines and aryl halides, rendering a diverse transformation. A series of mechanistic experiments and density functional theory (DFT) calculations were used to investigate the preferred pathway for this twofold C-H activation process.

Transition metal-catalyzed carbene transfer reaction is one of the most notable advances for C−C bond formation reactionsduring the past decade, which has been widely employed in the preparation of C3-substituted indoles. Here, we described an efficient example of catalyst- and metal-free aminoboration of alkynes and C C bond formation with diazo compounds to produce C3-substituted indoles. Diverse alkynylanilines and diazo compounds can be utilized for this tandem transformation under mild reaction conditions, resulting in broad functional group compatibility. Additionally, this metal-free strategy can be extended to construct substituted benzofurans.

We have developed a modular, convenient and practical copper-catalyzed platform for the preparation of alkene nitriles from corresponding cycloketoxime esters via radical-mediated C–C bond cleavage. A broad scope of cycloketoxime esters (4-membered to 8-membered) and some complex substrates derived from natural product derivatives performed well, affording corresponding ring opening products in the presence of copper salts. Moreover, the etherification, oxidation and alkynylation of cycloketoxime esters could also be achieved under variable copper-catalyzed conditions.

The formation of C-aryl bonds has been the focus of intensive research over the last decades for the construction of complex molecules from simple, readily available feedstocks. Traditionally, these strategies involve the coupling of organohalides (I, Br, Cl) with organometallic reagents (Mg, Zn, B, Si, Sn,…) such as Kumada-Corriu, Negishi, Suzuki-Miyaura, Hiyama and Sonogashira cross-couplings. More recently, alternative methods have provided access to these products by reactions with less reactive C-Het (F, O, S, N) and C-C bonds. Compared to traditional methods, the direct cleavage and arylation of these chemical bonds, the essential link in accessible feedstocks, has become increasingly important from the viewpoint of step-economy and functional-group compatibility. This comprehensive review aims to outline the development and advances of this topic, which was organized into (1) C-F bond arylation, (2) C-O bond arylation, (3) C-S bond arylation, (4) C-N bond arylation, and (5) C-C bond arylation. Substantial attention has been paid to the strategies and mechanistic investigations. We hope that this review can trigger chemists to discover more efficient methodologies to access arylation products by cleavage of these C-Het and C-C bonds.

The site-selective C-H bond functionalization of heteroarenes can eventually provide chemists with great techniques for editing and building complex molecular scaffolds. During the past decade, benzo-fused N-heterocycles such as indoles and quinolines have been among the most widely investigated organic templates. Early developments have led to site-selective C-H bond functionalization on the pyrrole and pyridine cores of indoles and quinolines; however, C-H functionalization on the benzenoid ring has remained a great challenge in catalysis. In this review, we elaborate on recent developments in the highly challenging functionalization of C-H bonds on the less-reactive benzenoid core of indoles and quinolines. These findings are mainly described as selective directing group assisted strategies, remote C-H functionalization techniques and their reaction mechanisms. The underlying principle in each strategy is elucidated, which aims to facilitate the design of a more advanced structure of heterocycles based on bioactive molecules, synthetic drugs, and material aspects. Moreover, the challenges and perspectives for catalytic C-H functionalization to access the arene backbone of indoles and quinolines are also proposed in the conclusion section.

Organophosphines are an important class of ligands widely used in organic chemistry. Although great progress has recently been made in the rapid construction of new phosphines through Rh- or Ru-catalyzed C–H bond functionalizations, synthetic access to more diverse phosphines remains a challenge. We describe an efficient process for the rhodium-catalyzed phosphorus(III)-directed hydroarylation of internal alkynes to generate various alkenylated and 2′,6′-dialkenylated biarylphosphines with high selectivity. A range of diverse alkynes and phosphines were effectively prepared with broad functional-group compatibility under the optimized conditions. In addition, the developed protocol can be extended to modify chiral phosphine ligands, providing enantioenriched alkenylated phosphines without erosion of the enantiomeric excess.

A novel protocol for palladium-catalyzed fluoroarylation of 1,1-difluoroallenes was described here. The reaction proceeded smoothly under mild condition and various trifluoromethylated alkenes were obtained in moderate yields with excellent E selectivity. The mechanism involving a vital trifluoromethylated vinyl silver intermediate, which generated through the F-nucleophilic addition to 1,1-difluoroallenes, has been proposed.

An efficient method for photocatalytic perfluoroalkylation of vinyl-substituted all-carbon quaternary centers involving 1,2-aryl migration has been developed. The rearrangement reactions use fac-Ir(ppy)3 , visible light and commercially available fluoroalkyl halides and can generate valuable multisubstituted perfluoroalkylated compounds in a single step that would be challenging to prepare by other methods. Mechanistically, the photoinduced alkyl radical addition to an alkene leads to the migration of a vicinal aryl substituent from its adjacent all-carbon quaternary center with the concomitant generation of a C-radical bearing two electron-withdrawing groups that is further reduced by a hydrogen donor to complete the domino sequence.

The first aromatic C-H silylation between arylphosphines and hydrosilanes enabled by a ruthenium complex has been developed. The excellent ortho-selectivity results from a four-membered metallacyclic intermediate involving phosphorus chelation. The developed system can be extended to the benzylic C-H silylation of arylphosphines. Diverse silylated arylphosphines are produced, exhibiting broad functional group compatibility. Further functionalization of the products under mild conditions renders the formed compounds useful building blocks.

Methyl group is not only an important building block of biologically active molecules and drug molecules, but also the important structural unit of complex molecules. Methylation of complex molecules is generally achieved through methylating reactions, which mainly include nucleophilic attack, electrophilic attack, and radical pathways. This review summarized the literatures of the past few decades and covered commonly used methylating agents used in methylation. In this review, the recently developed new methylating agents and methylation reactions are highlighted, and the reaction mechanisms are also detailed discussed. We expect that this review will inspire others to devote their research in the field of methylation.

Transition metal-catalyzed C-H activation is a step-economical strategy for peptide functionalization. Herein, we report the method of late-stage peptide ligation and macrocyclization through rhodium-catalyzed alkylation of tryptophan residues at the C7 position. This method utilizes a N-P

Enantioenriched alcohols comprise much of the framework of organic molecules. Here, we first report that chiral nickel complexes can catalyze the intermolecular enantioselective addition of aryl iodides across aldehydes to provide diverse optically active secondary alcohols using zinc metal as the reducing agent. This method shows a broad substrate scope under mild reaction conditions and precludes the traditional strategy through the pre-generation of organometallic reagents. Mechanistic studies indicate that an in situ formed arylnickel, instead of an arylzinc, adds efficiently to aldehydes, forming a new C-C bond and a chiral nickel alkoxide that may be turned over by zinc powder.

Stereo- and enantioselective cross-electrophile coupling involving C-F bond activation is reported. Treatment of gem-difluoroalkenes with racemic benzyl electrophiles in the presence of a chiral nickel complex using B