Ruthenium-Catalyzed N-Alkylation of Amines with Alcohols under Mild Conditions Using the Borrowing Hydrogen Methodology

Abstract

Using a simple amino amide ligand, ruthenium-catalyzed one-pot alkylation of primary and secondary amines with simple alcohols was carried out under a wide range of conditions. Using the alcohol as solvent, alkylation was achieved under mild conditions, even as low as room temperature. Reactions occurred with high conversion and selectivity in many cases. Reactions can also be carried out at high temperatures in organic solvent with high selectivity using stoichiometric amounts of the alcohol.

Transition‐Metal‐Catalyzed Hydrogen‐Transfer Annulations: Access to Heterocyclic Scaffolds

“…An atom-economical practical method for the synthesis of highly substituted/functionalized pyrroles (47)w as achieved by ar uthenium-catalyzed three-component annulation of ketones,a mines,a nd vicinal diols [Eq. (14)]. [29] To derive better catalytic systems,v arious ruthenium catalysts,l igands, and bases were analyzed for the three-component annulation reaction.…”

“…= molecular sieves]. [14] Thes ame ruthenium complex was used along with Xantphos for the construction of the benzodiazepine core, which has many applications in medicinal chemistry,through consecutive hydrogen-borrowing steps using 2-aminobenzylalcohols and 1,2-amino alcohols (Scheme 1). Based on the identification of the intermediates 6 and 7 in the reaction mixture,the tandem reaction starts with the oxidation of the more reactive benzyl alcohol to an aldehyde through ab orrowing-hydrogen process.S ubsequent imine formation with the more reactive 1,2-amino alcohol leads to the N-alkylation of the benzyl alcohol.…”

A Ruthenium‐Based Catalytic System for a Mild Borrowing‐Hydrogen Process

“…[3][4][5] The majority of the reported procedures require high temperatures (Ͼ100°C) and long reaction times, [4] which makes this catalytic protocol unsuitable for thermally unstable molecules. [9] In this paper, we report our results relating to the efficient alkylation of arylamines using stoichiometric amounts of aliphatic and benzylic alcohols in the presence of tBuOK. [6,7] Following our interest in borrowing-hydrogen and hydrogen-autotransfer reactions, [8] we have investigated the possibility of carrying out the Ru-catalysed alkylation of amines with alcohols under mild conditions.…”

“…Recently, the first example of a Ru-catalysed N-alkylation of amines at 65°C (and even at room temperature) using the alcohol itself as the reaction solvent was published by Enyong and Moasser. [9] In this paper, we report our results relating to the efficient alkylation of arylamines using stoichiometric amounts of aliphatic and benzylic alcohols in the presence of tBuOK. The reaction takes place under mild reaction conditions in terms of reagent amounts, Ru catalyst loading, reaction time, and temperature.…”

Transition‐Metal‐Free Three‐Component Synthesis of Tertiary Aryl Amines from Nitro Compounds, Boronic Acids, and Trialkyl Phosphites

“…These include the Buchwald-Hartwig [6] or the Ullmann [7] reactions between anilines and (pseudo)aryl halides, the Chan-Evans-Lam amination of boronic acid derivatives, which can be carried out either on Nsubstituted anilines [8] or on secondary alkylamines, [9] N-alkylation reactions, [10][11][12][13] and reductive amination procedures, [14] the last two specific for secondary alkylamines. Besides, some hydroamination procedures of secondary anilines have also been reported.…”