Isoindolines and 1,2-dihydroisoquinolines are important building blocks in drug molecules, agrochemicals, and materials. Herein, a novel and efficient pH-mediated selective Ir-catalyzed cascade reductive cyclization of 2-ethynylbenzaldehyde by coupling with aryl amines was realized. Using HCOOH as the hydride donor at low pH (1-2) in H2O media, the isoindoline products were obtained exclusively, while 1,2-dihydroisoquinoline products were formed preferentially by employing HCOONa as the hydride donor at high pH (9-10) using DMF as solvent. A wide range of functional groups, including electron-rich as well as electron-poor substituents on the aryl group of 2-ethynylbenzaldehyde and aryl amines, can be tolerated, affording the corresponding products in moderate to good yields. The practicality of this sustainable process was evidenced by large-scale experiment. Our mechanistic investigations indicate that the pH value is critical to the chemoselectivity.

Given the importance of the N-heterocyclics and carboxylic acids, methods for editing these skeletons would be specifically valuable in drug discovery. In this work, we report a tandem Ir-catalyzed transfer hydrogenation and N-alkylation of N-heteroarenes with carboxylic acids as alkylated sources, which efficiently produces a series of N-alkylated tetrahydroquinolines and heterocycles in moderate to excellent yields (up to 96%) under air conditions. A wide range of carboxylic acids, including complex drug molecules and natural products, can be served as alkylated sources and incorporated into N-heteroarenes to afford a variety of useful structure motifs (66 examples). The successful gram-scale transformation, as well as diversification of natural molecules and drugs further highlight the practicality and robustness of this strategy, holding broad potential for the synthesis of bioactive N-alkylated heterocyclics from renewable feedstock.

The formation of C-C and C-N bonds is an effective means to construct functional complex molecules. Herein, the TsOH-promoted dehydroxylation coupling of diarylmethanols with 1,3-dicarbonyls and sulfonamides to afford a variety of N-alkylated1,3-dicarbonyls and sulfonamides was established with only H2O as the byproduct. Differential 1,3-dicarbonyls and sulfonamides, including pharmaceutical molecules (sulfinpyrazone, phenylbutazone, mofebutazone, celecoxib, topiramate, valdecoxib) were compatible with this system to couple with alcohols in moderate to excellent yields. This method shows the merits of wide substrate scope and mild conditions.

Direct catalytic reductive hydroamination of alkynes enables C-N bond formation. In comparison with traditional reductive hydroamination of alkynes with amines, using nitroarenes as amine sources remains underdeveloped. Herein, we report a new and practical Ir-catalyzed muti-step tandem reductive hydroamination of alkynes with nitroarenes, delivering a series of aromatic amines in good yields (up to 96 %) under mild conditions. In addition, the alkynes can be incorporated into nitro-substituted bioactive molecules and are readily realized structural modification.

Herein, we advance a novel and efficient iridium-catalyzed transfer hydrogenation and N-alkylation of alkynyl/ alkenyl arylamines with carbonyls to facilitate the streamlined synthesis of diverse amines. The reaction could be achieved direct hydrogenation and alkylation of alkynyl/alkenyl arylamines with carbonyls using H2O as reaction media and HCO2H as hydrogen donor, providing a variety of arylamine derivatives in moderate to excellent yields. Control experiments indicated the N-alkylation of alkynyl/alkenyl arylamines contributed to the reduction of alkynes/alkenes. The practicality of this sustainable process was evidenced by large-scale, catalyst recycling experiments and derivatization of biologically active molecules.

Compared with other inexpensive metals-based catalysts for transfer hydrogenation, the use of manganese is rather more limited. Herein, a series of N, N-Mn(I)-Catalysts based on previous work were synthesized for transfer hydrogenation of ketones. Differential aromatic, heterocyclic ketones, as well as aliphatic ketones could be employed in this catalytic system, delivering the desired alcohol products in moderate to excellent yields. This N, N-Mn(I)-based catalytic system provides an alternative protocol for transfer hydrogenation of ketones to produce alcoholic products.

Selective functionalization has numerous potential applications in the modification of bioactive compounds and pharmaceuticals. Herein, we advance a new approach for the selective reductive N-formylation of N-heteroarenes and transfer hydrogenation using IrIII complexes as catalysts. The combination of solvent, equivalent of formic acid (FA), reaction temperature, and iridium catalyst exerts high product selectivity, delivering divergent selective formations of reductive N-formylation and transfer hydrogenation products in excellent yields. In this process, FA can be employed as not only the hydrogen source but also the reductive N-formylation reagent under different reaction conditions.

3,4-Dihydroquinolones are fundamental motifs widely found in a variety of natural products and drug molecules. Conventional methods for their synthesis suffer from the disadvantages of harsh reaction conditions and inefficiency, as well as selectivity issues. Herein, we develop a practical and efficient platform for the synthesis of 3,4-dihydroquinolones through successive hydrolysis and transfer hydrogenation processes. A wide range of 2-chloroquinolines and other substrates were compatible with this catalytic system and were converted into the corresponding products in moderate to excellent yields. The scale-up experiment and late-stage functionalization performance verified the practical use of this protocol. A practical and efficient platform for the synthesis of 3,4-dihydroquinolones through successive hydrolysis and transfer hydrogenation was presented. A wide range of 2-chloroquinolines were compatible with this catalytic system in excellent yields.

Here, we report a practical method to selectively access silylated pyrrolo[1,2-a]indoles using alkenyl indoles and readily available silanes through a radical cascade cyclization. The reaction proceeds through an unusual intermolecular polarity-mismatched addition of a nucleophilic silyl radical to e-rich alkene SOMOphiles via a coordination-assisted interaction. The scope and functional group compatibility of the protocol as well as a detailed mechanistic investigation are presented. A practical method to access silylated pyrrolo[1,2-a]indoles through an unusual intermolecular polarity-mismatched addition of a nucleophilic silyl radical to e-rich alkene SOMOphiles via a coordination-assisted interaction are presented.

Construction of arylmethanes is one of the forefronts and significant subjects in the field of organic synthesis due to the prevalence of this motifs in pharmaceuticals and biological compounds. Herein, an iridium-catalyzed deoxygenative cross-coupling of aryl ketones with anilines/phenols was established to synthesize diverse collections of arylmethanes. This process generates benzyl carbocationic intermediates from a wide range of aryl ketones, which were captured with anilines/phenols to access the corresponding arylmethanes under mild conditions. The fluorene compounds were also successfully afforded using ortho-substituted aryl ketones as inputs via intermolecular deoxygenative cross-coupling. This method is viable for applications in cross-coupling of complex bioactive molecules and drugs by this iridium-catalyzed deoxygenative cross-coupling process.

N-aryl-substituted pyrrolidines are important moieties widely found in bioactive substances and drugs. Herein, we present a practical reductive amination of diketones with anilines for the synthesis of N-aryl-substituted pyrrolidines in good to excellent yields. In this process, the N-aryl-substituted pyrrolidines were furnished via successive reductive amination of diketones via iridium-catalyzed transfer hydrogenation. The scale-up performance, water as a solvent, simple operation, as well as derivation of drug molecules showcased the potential application in organic synthesis.

Formamides are fundamental motifs that are prevalent in drugs, pesticides, dyes, and fragrances. Herein, we described an iridium-catalyzed Leuckart-type reductive amination of carbonyls, delivering formamides in moderate to excellent yields. In this process, ammonium formate was used as the N-formylating reagent to produce the formamide products. This protocol provides a new procedure for formamide synthesis.

Allylic amination is a powerful tool for constructing N-allylic amines widely found in bioactive molecules. Generally, allylic alcohols and unsaturated hydrocarbons have been considered for allylic amination reactions to minimize waste production. Herein, we present an iridium-catalysed method for reductive allylic amination of alpha,beta-unsaturated aldehydes with amines to afford N-allylic amines under air conditions. This protocol is demonstrated to provide products from many substrates (41 examples) in moderate-to-excellent yields. This synthetic methodology is also highlighted by the synthesis of drug molecules, optically pure products, as well as scale-up experiments.

β- and γ-Amino alcohols are among the most significant structural motifs in pharmacologically active molecules and pharmaceuticals. Herein, a protocol for the construction of β- and γ-amino alcohols via reductive amination and transfer hydrogenation of diketones with aromatic amines is described. This reaction is performed by utilizing iridium complexes as catalysts and HCO2H as a hydrogen donor to deliver a library of β- and γ-amino alcohols under mild and operationally simple conditions. Successful scale-up performance was also conducted under standard conditions.

The formation of C-N bond is a vital synthetic tool for establishing molecular diversity, which is highly sought after in a wide range of biologically active natural products and drugs. Herein, we present a new strategy for the synthesis of secondary amines via iridium-catalyzed one-pot reductive amination of carbonyl compounds with nitro compounds. This method is demonstrated for a variety of carbonyl compounds, including miscellaneous aldehydes and ketones, which are compatible with this catalytic system, and deliver the desired products in good yields under mild conditions. In this protocol, the reduction of nitro compounds occurs in situ first, followed by reductive amination to form amine products, providing a new one-pot procedure for amine synthesis.

The general protocol for site-specific alkylation of anilines and phenols would provide an ideal strategy for affording densely functionalized aniline and phenol derivatives. Herein, we disclose a new iridium-catalyzed and acid-promoted process for selective para-alkylation of anilines and phenols using aryloxy or alkoxy aryl alkynes as the alkylated sources, delivering a wide range of para-C-alkylated phenols and anilines in good to excellent yields. The low catalyst loading (up to 0.05 mol%), scale-up of synthesis, operation under air conditions, as well as recycling of catalyst (5 times without deactivation) evidenced the promising application in organic synthesis.

Herein, we report an efficient one-pot iridium-catalyzed reductive hydroamination of terminal alkynes with amines. A variety of primary amines and secondary amines are amenable to this catalytic system, leading to the complicated aliphatic amines in excellent yields. More broadly, this straightforward and convenient transformation do not just employ inexpensive and easy to handle HCO2H as reducing agent, but also employs H2O as reaction media, which makes this strategy be in accordance with green and sustainable chemistry principles.

The difluoroalkylation of unactivated alkenes with ethyl iododifluoroacetate via visible light-induced process has been developed. This transformation provides selective access to difluoroalkylated indole derivatives in good yields depending on the choice of base, solvent, as well as the loading of ethyl iododifluoroacetate.

氟烷基杂环化合物广泛存在于天然产物和药物分子中,在药物化学和临床治疗上有着极其重要的作用.因此,高效构筑氟烷基杂环一直是合成方法学研究的热点之一.目前化学合成氟烷基杂环化合物的方法主要有:直接碳-氢活化芳杂环、过渡金属催化作用下卤代杂环与氟试剂的交叉偶联反应、氟烷基取代杂环参与的交叉偶联反应以及烯烃与氟烷基试剂的串联环化反应.本文对近年来氟烷基化合物的合成研究进展进行了归纳与总结,为氟烷基杂环化合物的设计合成提供参考依据.

An efficient Fe-catalyzed electrochemical synthesis of benzothiazoles from ethers with 2-aminobenzenethiols has been developed through selective C-O bond cleavage of ethers under oxidant-free conditions. A set of ethers have been converted to the corresponding 2-aryl-, 2-heteroaryl-, and 2-alkyl-substituted benzothiazoles in moderate to good yields. The method has also been successfully applied to generation of benzimidazoles and benzoxazoles with satisfactory yields and good functional group compatibility.