Selective Synthesis of Amides and α-Ketoamides via Electrochemical Decarboxylation and Dehydration.

An electrochemical and selective decarboxylation and dehydration using α-keto acids with amines is accomplished, which leads to the easy accessibility of amides and α-ketoamides, which are not only ubiquitous and valuable structure motifs found in pharmaceuticals, but also versatile building blocks in synthetic chemistry. Notably, for this efficient and green protocol, neither metal catalysts nor external oxidants are required. The process exhibits a broad scope and functional group tolerance to deliver various amides and α-ketoamides. Moreover, these two reactions have also been applied to late-stage derivatization and can be safely conducted on gram scale.

Electrochemical oxidative thioetherification of aldehyde hydrazones with thiophenols.

An electrochemically promoted oxidative dehydrogenation cross-coupling reaction between aldehyde hydrazones and thiophenols is demonstrated for the first time, which resulted in a variety of (Z)-thioetherified products in moderate to excellent yields. This strategy can be carried out under an air atmosphere, featuring scalability and excellent stereoselectivity. In addition, the transformation efficiently produces readily recyclable disulfide as a by-product with high yields, which significantly reduces the environmental pollution caused by thioetherification.

A Palladium-Catalyzed Carbonylative Acetylation of N-Phenylpyridin-2-amine Using DMF and CO as the Acetyl Source.

This study reports a carbonylative acetylation for the synthesis of N-phenyl-N-(pyridin-2-yl)acetamides using N,N-dimethylformamide (DMF) as a methyl source and CO as a carbonyl source. Interestingly, dimethyl sulfoxide (DMSO) can be also used as a methyl source when using only DMSO as the solvent. Mechanistic studies using DMSO-d6 revealed that the methyl group was derived from the methyl group of DMF instead of DMSO when using DMF and DMSO as a mixed solvent. These results indicated that DMF was a preferential methyl source.

Copper-Catalyzed Sulfonylation Reaction of NH-Sulfoximines with Aryldiazonium Tetrafluoroborates and Sulfur Dioxide: Formation of N-Sulfonyl Sulfoximines.

An efficient and practical SO2 insertion protocol of NH-sulfoximines with aryldiazonium tetrafluoroborates and DABSO toward N-sulfonyl sulfoximines has been developed under mildly basic conditions. This transformation features easy operation, readily available substrates, and mild conditions. A tentative mechanism is proposed, which indicates that the aryldiazonium tetrafluoroborates would be radical donors under standard reaction conditions. The aryl radical produced in situ from diazonium salts would be trapped by SO2 to generate an arylsulfonyl radical and then undergo further transformation to generate the final N-sulfonyl sulfoximines.

Electrochemically Driven Selective Removal of the S═N Bond-Directing Group Using Cyclohexanone Oxime as the Mediator.

An inexpensive electrochemical induction system was used for the efficient reductive defunctionalization of sulfoximines through a radical pathway. This practical and robust strategy could be used for the removal of the S═N bond-directing group from various sulfoximines. The practicability of this method was demonstrated by its mild conditions, simple operation, one-pot procedure, gram-scale synthesis, and the undivided cell. Furthermore, preliminary mechanistic studies suggested that the reaction might proceed via a homocoupling reaction and a denitrification procedure.

Electrochemical N-Acylation of Sulfoximine with Hydroxamic Acid.

Despite the widespread applications of sulfoximines, green and efficient access to functionalized sulfoximines remains a challenge. By employing an electrochemical strategy, we describe an approach for the construction of N-aroylsulfoximines, which features a broad substrate scope, mild reaction conditions, safety on a gram scale, and no need for an external oxidant and transition metal catalysts.

Selective Electrochemical Halogenation of Functionalized Quinolone.

This work describes an effective C3-H halogenation of quinoline-4(1H)-ones under electrochemical conditions, in which potassium halides serve as both halogenating agents and electrolytes. The protocol provides expedient access to different halogenated quinoline-4(1H)-ones with unique regioselectivity, broad substrate scope, and gram-scale synthesis employing convenient, environmentally friendly electrolysis, in an undivided cell. Mechanism studies have shown that halogen radicals can promote the activation of N-H bonds in quinolones.

Oxidative C-H/N-H Carbonylation of Benzamide by Nickel Catalysis with CO as the Carbonyl Source.

An efficient and direct carbonylation of aminoquinoline benzamides has been developed using abundant and inexpensive Ni(OAc)2·4H2O as the catalyst and carbon monoxide as a cost-efficient C1 building block. This process features good functional-group tolerance and can be conducted on gram scale. The directing group can be easily removed under mild conditions.

Palladium-Catalyzed Multistep Tandem Carbonylation/N-Dealkylation/Carbonylation Reaction: Access to Isatoic Anhydrides.

A novel and efficient synthesis of isatoic anhydride derivatives was developed via palladium-catalyzed multistep tandem carbonylation/N-dealkylation/carbonylation reaction with alkyl as the leaving group and tertiary anilines as nitrogen nucleophiles. This approach features good functional group compatibility and readily available starting materials. Furthermore, it provided a convenient approach for the synthesis of biologically and medicinally useful evodiamine.

Copper- and DMF-mediated switchable oxidative C-H cyanation and formylation of imidazo[1,2-a]pyridines using ammonium iodide.

The cyanation and formylation of imidazo[1,2-a]pyridines were developed under copper-mediated oxidative conditions using ammonium iodide and DMF as a nontoxic combined cyano-group source and DMF as a formylation reagent. Mechanistic studies indicate that the cyanation of imidazo[1,2-a]pyridines proceeds through a two-step sequence: initial iodination and then cyanation. The cyanation has a broad substrate scope and high functional group tolerance, and can be safely conducted on a gram scale. A novel copper-mediated formylation using the widely available DMF as the formylation reagent and environmentally friendly molecular oxygen as the oxidant has also been developed. This protocol also provided a convenient approach for the synthesis of clinically used saripidem.

Carbonylation Access to Phthalimides Using Self-Sufficient Directing Group and Nucleophile.

Herein we report a novel palladium-catalyzed oxidative carbonylation reaction for the synthesis of phthalimides with high atom- and step-economy. In our strategy, the imine and H2O, which are generated in situ from the condensation of aldehyde and amine, serve as self-sufficient directing group and nucleophile, respectively. This method provides rapid access to phthalimides starting from readily available materials in a one-pot manner. Various phthalimide derivatives are constructed efficiently, including medicinally and biologically active phthalimide-containing compounds.

A Four-Component Reaction Strategy for Pyrimidine Carboxamide Synthesis.

Demonstrated herein is a highly effective 3 starting materials-4 component reaction (3SM-4CR) strategy for the synthesis of pyrimidine carboxamides from amidines, styrene, and N,N-dimethylformamide (DMF) by a palladium-catalyzed oxidative process. This transformation represents the first example of employing DMF as a dual synthon, a one-carbon-atom synthon and amide synthon, and was proven by isotope-labeling experiments. Additionally, the combination of C-H bond functionalization and cross-dehydrogenative coupling processes affords four chemical bond formations. This sequential 3SM-4CR strategy features inexpensive, readily available starting materials, green oxidants, as well as atom and step economy. It leads to the preparation of pyrimidine carboxamides and has potential applications in the pharmaceutical industry.

Transition Metal Free Intermolecular Direct Oxidative C-N Bond Formation to Polysubstituted Pyrimidines Using Molecular Oxygen as the Sole Oxidant.

Various polysubstituted pyrimidines are smoothly formed via a base-promoted intermolecular oxidation C-N bond formation of allylic C(sp(3))-H and vinylic C(sp(2))-H of allyllic compounds with amidines using O2 as the sole oxidant. This protocol features protecting group free nitrogen sources, good functional group tolerance, high atom economy, and environmental advantages.

Palladium-Catalyzed Oxidative O-H/N-H Carbonylation of Hydrazides: Access to Substituted 1,3,4-Oxadiazole-2(3H)-ones.

A novel palladium-catalyzed oxidative annulation reaction for the C-O, C-N bond formations is developed. The intramolecular cyclocarbonylation provides an efficient and direct approach for the construction of valuable 1,3,4-oxadiazole-2(3H)-ones and their derivatives. The reaction also facilitated the convenient synthesis of BMS-191011, an opener of the cloned large-conductance Ca(2+)-activated potassium channel, providing an attractive method for medicinal chemistry.

Base-mediated decomposition of amide-substituted furfuryl tosylhydrazones: synthesis and cytotoxic activities of enynyl-ketoamides.

Base-mediated decomposition of amide-substituted furfuryl tosylhydrazones afforded practical access to novel multifunctionalized enynyl-ketoamides. In addition, furfuryl tosylhydrazones with stable furan rings underwent an interesting tosyl-group migration to form sulfones, which have potential synthetic applications. Some of the obtained enynyl-ketoamides demonstrated good cytotoxicities against human tumor cell lines.

Palladium-catalyzed oxidative carbonylation for the synthesis of polycyclic aromatic hydrocarbons (PAHs).

A direct and facile palladium-catalyzed C-H bond oxidative carbonylation reaction and oxidative cyclization for the synthesis of polycyclic aromatic hydrocarbons (PAHs) is reported herein. The intramolecular cyclocarbonylation, through C-H activation and C-C, C-O bond formations under mild conditions, proceeds smoothly with good functional group tolerance in high to excellent yields. The intramolecular palladium-catalyzed direct oxidative C-H bond functionalization for the C-O bond formation is also demonstrated, which provides an efficient approach for the construction of various PAHs.

Electrochemical Oxidative Carbonylation of NH-Sulfoximines.

The electrochemical synthesis of N-aroylsulfoximines features the use of tetra-n-butylammonium iodide (TBAI) as the medium and a broad substrate scope, thus affording a wide range of N-aroylated sulfoximines in moderate to good yields. The advantages of this electrochemical strategy are augmented by mild reaction conditions that are external oxidant-free, ligand-free, and easy to scale up to gram scale. Both the control experiments and the mechanistic studies revealed that the whole electrochemical process proceeded through a palladium (II/IV/II) catalytic cycle.

Cu(II)-promoted transformations of α-thienylcarbinols into spirothienooxindoles: regioselective halogenation of dienyl sulfethers containing electron-rich aryl rings.

Under the promotion of Cu(II) salts, the α-thienylcarbinols with an N-phenyl carbonyl group at the other α-position are converted into three different ranges of spirothienooxindoles involving dearomatizing Friedel-Crafts reaction. In addition, the unprecedented regioselective CuX(2)-mediated C-H functionalization/halogenation of dienyl sulfether containing electron-rich aryl rings is presented.

Copper-Catalyzed Divergent C-H Functionalization Reaction of Quinoxalin-2(1H)-ones and Alkynes Controlled by N1-Substituents for the Synthesis of (Z)-Enaminones and Furo[2,3-b]quinoxalines.

With control by N1-substituents, the switchable divergent C-H functionalization reaction of quinoxalin-2(1H)-ones is achieved for the synthesis of (Z)-enaminones and furo[2,3-b]quinoxalines using the combination of a copper catalyst and an oxidant. This new protocol features mild reaction conditions, readily available materials, and a broad substrate scope. Gram-scale and mechanistic studies were also investigated. Furthermore, the desired products exhibited excellent antitumor activity against A549, HepG-2, MCF-7, and HeLa cells, which were tested by MTT assay.

A facile approach to synthesize 3,5-disubstituted-1,2,4-oxadiazoles via copper-catalyzed-cascade annulation of amidines and methylarenes.

Various 3,5-disubstituted-1,2,4-oxadiazoles are smoothly formed via copper-catalyzed cascade annulation of amidines and methylarenes. This tandem oxidation-amination-cyclization transformation represents a straightforward protocol to prepare 1,2,4-oxadiazoles from easily available starting materials, with inexpensive copper catalysts and green oxidants. It has the advantages of atom- and step-economy, good functional group tolerance, as well as operational simplicity.