Metal-Free Cyanation of gem-Difluoroalkenes via Azide-Mediated C-C Double Bond Fragmentation.

Activation and cleavage of C-C double bonds are long-standing challenges in synthetic chemistry. Herein, we report an unprecedented azide-mediated C-C double bond fragmentation of gem-difluoroalkenes under mild and metal-free conditions, enabling the efficient synthesis of structurally diverse aromatic nitriles in moderate to good yields. This protocol is also amenable to the cyanation of gem-dichloro and dibromo alkenes. This reaction features simple operation and good functional group compatibility and can be implemented at a gram scale.

Ag-Catalyzed Practical Synthesis of N-Acyl Anthranilic Acids from Anthranils and Carboxylic Acids.

A practical synthesis of valuable N-acyl anthranilic acids has been achieved via a silver-catalyzed imino-ketene generation from readily available anthranils and carboxylic acids. A wide range of carboxylic acids including sterically demanding aliphatic carboxylic acids, aromatic carboxylic acids, acrylic acids, and amino acids are compatible in this reaction. Moreover, this method can be used to modify drug molecules and natural products, such as ibuprofen, probenecid, and acetylglycine.

Tf2O-Promoted Chemoselective C3 Functionalization of Anthranils with Phenols and Thiophenols.

Different chemoselectivities of phenols and thiophenols were observed in a Tf2O-promoted C3 functionalization of simple anthranils. The reaction of phenols and anthranils gives 3-aryl anthranils via a C-C bond formation, whereas thiophenols afford 3-thio anthranils through a C-S bond formation. Both reactions have a broad substrate scope and tolerate a wide range of functional groups, affording the corresponding products with specific chemoselectivity.

Practical synthesis of isocoumarins via Rh(III)-catalyzed C-H activation/annulation cascade.

Herein, we report an unprecedented Rh(III)-catalyzed C-H activation/annulation cascade of readily available enaminones with iodonium ylides towards the convenient synthesis of isocoumarins. This coupling system proceeds in useful chemical yields (up to 93%) via a cascade C-H activation, Rh-carbenoid migratory insertion and acid-promoted intramolecular annulation. The success of gram-scale reaction and diverse functionalization of isocoumarins demonstrated the synthetic utility of this protocol.

NiH-Catalyzed Proximal-Selective Hydroamination of Unactivated Alkenes with Anthranils.

The regioselective hydroamination of unactivated alkenes is a long-standing challenge in organic synthesis. Herein, we report a NiH-catalyzed proximal-selective hydroamination of unactivated alkenes with 8-aminoquinoline (AQ) as a bidentate auxiliary and anthranils as aminating reagents. A wide range of primary aryl amines bearing an ortho-carbonyl group were installed in both terminal and internal unactivated alkenes, delivering a variety of valuable ß- and γ-amino acid building blocks, respectively, with excellent regiocontrol. The utility of this transformation was further demonstrated by the conversion of the multifunctionalized aryl amines into useful N-heterocycles.

[Meta-analysis of Shenqi Jiangtang Granules combined with western medicine on adverse pregnancy outcomes in women with gestational diabetes mellitus].

The present study evaluated the effect of Shenqi Jiangtang Granules(SJG) combined with western medicine on the adverse pregnancy outcomes in women with gestational diabetes mellitus(GDM). PubMed, Web of Science, CNKI, Wanfang, and VIP were searched for clinical randomized controlled trials(RCTs) of SJG combined with western medicine against GDM. The included RCTs were assessed for risks using the assessment criteria recommended by the Cochrane handbook for systematic reviews of interventions. Meta-analysis was performed using Stata 12.0 and RevMan 5.3. Nineteen RCTs were included, with 1 647 patients involved, including 824 cases treated with western medicine alone, and 823 cases treated with SJG combined with western medicine. The course of treatment ranged from 2 to 12 weeks. As revealed by Meta-analysis results, compared with western medicine treatment alone, SJG combined with western medicine could reduce the incidence of postpartum hemorrhage(OR=0.23, 95%CI[0.10, 0.53], P=0.000 6), gestational hypertension(OR=0.24, 95%CI[0.13, 0.45], P<0.000 01), polyhydramnios(OR=0.24, 95%CI[0.12, 0.45], P<0.000 1), premature rupture of membranes(OR=0.20, 95%CI[0.09, 0.45], P<0.000 1), cesarean section(OR=0.40, 95%CI[0.29, 0.55], P<0.000 01), macrosomia(OR=0.19, 95%CI[0.08, 0.47], P<0.000 3), neonatal asphyxia(OR=0.22, 95%CI[0.12, 0.40], P<0.000 01), premature delivery(OR=0.19, 95%CI[0.12, 0.30], P<0.000 01), proteinuria(OR=0.19, 95%CI[0.06, 0.58], P=0.004) and hypoglycemia(OR=0.28, 95%CI[0.16, 0.50], P<0.000 1). The funnel plots and Egger's test showed that except macrosomia, there was no significant publication bias in the results of other indicators. Therefore, as indicated by the findings, SJG combined with western medicine can reduce the incidence of adverse pregnancy outcomes in GDM patients. However, due to the uneven quality of the included trials, the clinical application of this protocol requires caution.

Nickel-Catalyzed Hydroamination of Olefins with Anthranils.

A nickel-catalyzed polarity-reversed hydroamination of olefins has been achieved with anthranils as the electrophilic aminating agents and hydrosilane as the reductant. This protocol provides a facile access to N-alkyl-2-aminobenzophenones that are versatile intermediates in organic synthesis. A wide range of olefins and anthranils are compatible in this transformation, delivering the desired amines in useful to excellent yields (38 examples, up to 92% yield). The utility of this protocol is exhibited in the late-stage functionalization of drug molecules and the valuable derivatives of the obtained amination products.

Copper-Catalyzed Electrophilic Amination of Arylboronic Acids with Anthranils: An Access to N-Aryl-2-aminophenones.

An efficient copper-catalyzed electrophilic amination strategy has been established for the rapid synthesis of N-aryl-2-aminophenones from readily available arylboronic acids/esters and anthranils. This protocol features good functional group tolerance, broad substrate scope, and operational simplicity. Moreover, a tandem C-H borylation and C-N coupling protocol has also been developed to transform simple arenes to the valuable N-aryl-2-aminophenones in one pot. Additionally, the synthetic potential of this methodology is further demonstrated by the synthesis of various useful N-heterocycles and derivatives.

Recent Advances in Catalytic Synthesis of Benzosultams.

Benzosultams represent one category of multi-heteroatom heterocyclic scaffolds, which have been frequently found in pharmaceuticals, agricultural agents, and chiral catalysts. Given the diversely significant functions of these compounds in organic and medicinal chemistry, great efforts have been made to develop novel catalytic systems for the efficient construction of benzosultam motifs over the past decades. Herein, in this review, we mainly summarize the recent advances in the field of catalytic synthesis of benzosultams from 2017 to August of 2020, with an emphasis on the scopes and mechanisms of representative reactions.

Exploration of Visible-Light Photocatalysis in Heterocycle Synthesis and Functionalization: Reaction Design and Beyond.

Visible-light photocatalysis has recently received increasing attention from chemists because of its wide application in organic synthesis and its significance for sustainable chemistry. This catalytic strategy enables the generation of various reactive species, frequently without stoichiometric activation reagents under mild reaction conditions. Manipulation of these reactive intermediates can result in numerous synthetically useful bond formations in a controllable manner. In this Account, we describe our recent advances in the rational design and strategic application of photocatalysis in the synthesis of various synthetically and biologically important heterocycles. Our main research efforts toward this goal can be classified into four categories: formal cycloaddition and cyclization reactions, radical-mediated olefin functionalization/cyclization cascades, photocatalytic generation and cyclization of N-centered radicals, and photocatalytic functionalization of heterocycles by visible-light-induced dual catalysis. Inspired by the wide application of tertiary amines as reductive additives in photoredox catalysis, we exploited a series of readily accessible or rationally designed tertiary amines with reactive sites in a range of photocatalytic formal cycloaddition and cyclization reactions, providing efficient access to diverse nitrogen heterocycles. Employing various photogenerated radical species, we further developed a series of radical-mediated olefin functionalization/cyclization cascade reactions to successfully assemble various five- and six-membered heterocycles. We have also achieved for the first time the direct catalytic conversion of recalcitrant N-H bonds into neutral N-centered radicals through a visible-light-photocatalytic oxidative deprotonation electron transfer. Using this generic strategy, we have devised several types of radical cyclizations of unsaturated hydrazones, leading to the construction of diversely functionalized pyrazoline and pyridazine derivatives in good yields and selectivity. Moreover, we have demonstrated that this photocatalysis can serve as a mild and highly selective tool for direct functionalization of heterocycles because of its powerful capability to controllably generate diverse reactive intermediates under mild reaction conditions. Guided by the fundamental principles of photocatalysis and the redox properties of the photocatalysts, we successfully developed an array of dual-catalyst systems by combining the photocatalysts with palladium, nickel, or amine, enabling efficient and selective coupling reactions. An intriguing phototandem catalytic system using a single photocatalyst was also identified for the development of cascade reactions. Notably, some of the newly developed methodologies have also been successfully utilized for late-stage modification of biologically active natural compounds and complex molecules and as key steps for formal synthesis of natural products. This Account presents a panoramic view and the logic of our recent contributions to the design, development, and application of photocatalytic systems and reactions that provide not only methods for the efficient synthesis of heterocycles but also useful insights into the exploration of new photochemical reactions.

Visible light photoredox-controlled reactions of N-radicals and radical ions.

Radicals are an important class of versatile and highly reactive species. Compared with the wide applications of various C-centred radicals, however, the N-radical species including N-centred radicals and radical ions remain largely unexplored due to the lack of convenient methods for their generation. In recent years, visible light photoredox catalysis has emerged as a powerful platform for the generation of various N-radical species and methodology development towards the synthesis of diverse N-containing compounds. In this tutorial review, we highlight recent advances in this rapidly developing area with particular emphases put on the working models and new reaction design.

Controllable Remote C-H Bond Functionalization by Visible-Light Photocatalysis.

Remote control: New strategies for the activation of remote C(sp3 )-H bonds by photoredox-catalyzed (PC) radical translocation via O- and N-centered radicals have recently been described. These methods enable the controlled and site-selective functionalization of inert C(sp3 )-H bonds and provide new opportunities for reaction design (HAT=hydrogen atom transfer).

Organophotocatalytic Generation of N- and O-Centred Radicals Enables Aerobic Oxyamination and Dioxygenation of Alkenes.

A cooperative TEMPO and photoredox catalytic strategy was applied for the first time to the direct conversion of N-H and O-H bonds into N- and O-centred radicals, enabling a general and selective oxidative radical oxyamination and dioxygenation of various ß,γ-unsaturated hydrazones and oximes. In the reaction, O2 was employed not only as a terminal oxidant but also as the oxygen source. This protocol provided efficient access to the synthesis of various synthetically and biologically important pyrazoline, pyridazine and isoxazoline derivatives under metal-free and mild reaction conditions. Mechanistic studies revealed that the cooperative organophotocatalytic system functions through two single-electron-transfer (SET) processes.

PhI(OAc)2-mediated functionalisation of unactivated alkenes for the synthesis of pyrazoline and isoxazoline derivatives.

A PhI(OAc)2-promoted radical cyclization of ß,γ-unsaturated hydrazones and oximes has been developed for an efficient synthesis of various valuable pyrazoline and isoxazoline derivatives with satisfactory yields (up to 96%) under mild conditions.

Enantioselective organocatalytic oxa-Michael addition of oximes to ß-CF3-ß-disubstituted nitroalkenes: efficient synthesis of ß-amino-α-trifluoromethyl alcohols.

An enantioselective oxa-Michael addition of oximes to ß-CF3-ß-disubstituted nitroalkenes catalyzed by a chiral bifunctional cinchona alkaloid-based thiourea has been developed. A variety of trifluoromethylated oxime ethers possessing a tetrasubstituted carbon stereocenter were obtained in good yields with high enantioselectivities.

Metal-containing carbonyl ylides: versatile reactants in catalytic enantioselective cascade reactions.

New players in town: In situ generated transition-metal-containing carbonyl ylides are a unique class of reagents which have found wide applications in catalytic asymmetric cascade reactions. Recent advances in reaction design are likely to lead to more novel developments with these reactive species.

Photocatalytic generation of N-centered hydrazonyl radicals: a strategy for hydroamination of ß,γ-unsaturated hydrazones.

A visible-light photocatalytic generation of N-centered hydrazonyl radicals has been accomplished for the first time. This approach allows efficient intramolecular addition of hydrazonyl radical to terminal alkenes, thus providing hydroamination and oxyamination products in good yields. Importantly, the protocol involves deprotonation of an N-H bond and photocatalytic oxidation to an N-centered radical, thus obviating the need to prepare photolabile amine precursors or the stoichiometric use of oxidizing reagents.

Iron-Catalyzed Photochemical Synthesis of Sulfinamides from Aliphatic Hydrocarbons and Sulfinylamines.

An iron-catalyzed photochemical sulfinamidation of hydrocarbons with N-sulfinylamines has been developed. The merger of ligand-to-metal charge transfer (LMCT) of FeCl3 with hydrogen atom transfer (HAT) process is the key for the generation of alkyl radicals from hydrocarbons, and the resultant alkyl radicals were readily trapped by N-sulfinylamines to produce structurally diverse sulfinamides. Contrary to traditional methods that inevitably use sensitive organometallic reagents and prefunctionalized substrates, our approach features simple operation and the wide availability of starting materials. Gratifyingly, the reaction is scalable, and the obtained sulfinamides can be conveniently converted to highly functionalized sulfur(VI) derivatives.

Expedient access to polysubstituted acrylamides via strain-release-driven dual phosphine and palladium catalysis.

Polysubstituted acrylamides are ubiquitous in bioactive molecules and natural products. However, synthetic methods for the assembly of these important motifs remain underdeveloped. Herein, we report the expedient synthesis of structurally diverse and synthetically challenging polysubstituted acrylamides from readily available aromatic amines, cyclopropenones (CpOs), and aryl halides via the synergistic merging of nucleophilic phosphine-mediated amidation and palladium-catalyzed C-H arylation. The reaction is scalable, and some obtained acrylamides proved to be solid state luminogens with obvious aggregation-induced emission (AIE) properties, demonstrating the synthetic potential in drug discovery and material development.

Radical-Mediated Decarboxylative C-C and C-S Couplings of Carboxylic Acids via Iron Photocatalysis.

Despite the significant success of decarboxylative radical reactions, the catalytic systems vary considerably upon different radical acceptors, requiring renewed case-by-case reaction optimization. Herein, we developed an iron catalytic condition that enables the highly efficient decarboxylation of various carboxylic acids for a range of radical transformations. This operationally simple protocol was amenable to a wide array of radical acceptors, delivering structurally diverse oxime ethers, alkenylation, alkynylation, thiolation, and amidation products in useful to excellent yields (>40 examples, up to 95% yield).