Practical methodologies for the synthesis of indoles.

Dehydrogenation as a substrate-activating strategy in homogeneous transition-metal catalysis.

Given the widespread importance of amides in biochemical and chemical systems, an efficient synthesis that avoids wasteful use of stoichiometric coupling reagents or corrosive acidic and basic media is highly desirable. We report a reaction in which primary amines are directly acylated by equimolar amounts of alcohols to produce amides and molecular hydrogen (the only products) in high yields and high turnover numbers. This reaction is catalyzed by a ruthenium complex based on a dearomatized PNN-type ligand [where PNN is 2-(di-tert-butylphosphinomethyl)-6-(diethylaminomethyl)pyridine], and no base or acid promoters are required. Use of primary diamines in the reaction leads to bis-amides, whereas with a mixed primary-secondary amine substrate, chemoselective acylation of the primary amine group takes place. The proposed mechanism involves dehydrogenation of hemiaminal intermediates formed by the reaction of an aldehyde intermediate with the amine.

http://science.sciencemag.org/content/sci/317/5839/790.full.pdf

Direct Synthesis of Amides from Alcohols and Amines with Liberation of H2

Conventional oxidations of organic compounds formally transfer hydrogen atoms from the substrate to an acceptor molecule such as oxygen, a metal oxide, or a sacrificial olefin. In acceptorless dehydrogenation (AD) reactions, catalytic scission of C-H, N-H, and/or O-H bonds liberates hydrogen gas with no need for a stoichiometric oxidant, thereby providing efficient, nonpolluting activation of substrates. In addition, the hydrogen gas is valuable in itself as a high-energy, clean fuel. Here, we review AD reactions selectively catalyzed by transition metal complexes, as well as related transformations that rely on intermediates derived from reversible dehydrogenation. We delineate the methodologies evolving from this recent concept and highlight the effect of these reactions on chemical synthesis.

http://science.sciencemag.org/content/sci/341/6143/1229712.full.pdf

Applications of acceptorless dehydrogenation and related transformations in chemical synthesis.

Hydrogen autotransfer in the N-alkylation of amines and related compounds using alcohols and amines as electrophiles.

Des aminoarenes sont transformes directement en amines secondaires et tertiaires par reaction a 150-180°C avec des alcools primaires en presence de catalyseurs complexes de Ru dont le plus actif est le dichloro-tris(triphenylphosphine)-Ru. Cinetique. On propose un cycle catalytique qui met en jeu une attaque nucleophile de l'aminoarene sur un aldehyde intermediaire

Ruthenium-catalyzed N-alkylation and N-benzylation of aminoarenes with alcohols

Ruthenium-complex-catalyzed N-heterocyclization. Syntheses of quinolines and indole derivatives from aminoarenes and 1,3-propanediol of glycols

Ruthenium complex catalyzed N-heterocyclization. Syntheses of N-substituted piperidines, morpholines, and piperazines from amines and 1,5-diols

Various nitroarenes having chloro, methyl, or methoxy substituents were reduced to the corresponding aminoarenes in high yields using formic acid in the presence of a catalytic amount of RuCl2(PPh3)3. For example, 4-chloronitrobenzene was converted in 99% conversion with 98% selectivity at 125 °C for 5 h. 4-Nitroacetophenone was reduced chemoselectively to 1-(4-nitrophenyl)ethanol in 74% isolated yield under the same reaction conditions. Formic acid could also be employed as reductant for hydrogenation of heterocyclic compounds such as quinoline, indole, and quinoxaline in the presence of the ruthenium catalyst. 2-Methylquinoline was hydrogenated to 1,2,3,4-tetrahydro-2-methylquinoline in 93% conversion with 100% selectivity.

Yasushi Tsuji

Papers

Ruthenium-catalyzed N-alkylation and N-benzylation of aminoarenes with alcohols

Ruthenium-complex-catalyzed N-heterocyclization. Syntheses of quinolines and indole derivatives from aminoarenes and 1,3-propanediol of glycols

Ruthenium complex catalyzed N-heterocyclization. Syntheses of N-substituted piperidines, morpholines, and piperazines from amines and 1,5-diols

Ruthenium Catalyzed Reduction of Nitroarenes and Azaaromatic Compounds Using Formic Acid

Palladium-catalyzed decarbonylative coupling of acid chlorides, organodisilanes, and 1,3-dienes