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

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

Alcohols can be temporarily converted into carbonyl compounds by the metal-catalysed removal of hydrogen. The carbonyl compounds are reactive in a wider range of transformations than the precursor alcohols and can react in situ to give imines, alkenes, and α-functionalised carbonyl compounds. The metal catalyst, which had borrowed the hydrogen, then returns it to the transformed carbonyl compound, leading to an overall process in which alcohols can be converted into amines, compounds containing CC bonds and β-functionalised alcohols.

Borrowing hydrogen in the activation of alcohols

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

Hitoshi Ige

Papers

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