Amide synthesis from alcohols and amines catalyzed by ruthenium N-heterocyclic carbene complexes. 2010

Johan Hygum Dam, and Gyorgyi Osztrovszky, and Lars Ulrik Nordstrøm, and Robert Madsen
Department of Chemistry, Building 201, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.

The direct synthesis of amides from alcohols and amines is described with the simultaneous liberation of dihydrogen. The reaction does not require any stoichiometric additives or hydrogen acceptors and is catalyzed by ruthenium N-heterocyclic carbene complexes. Three different catalyst systems are presented that all employ 1,3-diisopropylimidazol-2-ylidene (IiPr) as the carbene ligand. In addition, potassium tert-butoxide and a tricycloalkylphosphine are required for the amidation to proceed. In the first system, the active catalyst is generated in situ from [RuCl(2)(cod)] (cod=1,5-cyclooctadiene), 1,3-diisopropylimidazolium chloride, tricyclopentylphosphonium tetrafluoroborate, and base. The second system uses the complex [RuCl(2)(IiPr)(p-cymene)] together with tricyclohexylphosphine and base, whereas the third system employs the Hoveyda-Grubbs 1st-generation metathesis catalyst together with 1,3-diisopropylimidazolium chloride and base. A range of different primary alcohols and amines have been coupled in the presence of the three catalyst systems to afford the corresponding amides in moderate to excellent yields. The best results are obtained with sterically unhindered alcohols and amines. The three catalyst systems do not show any significant differences in reactivity, which indicates that the same catalytically active species is operating. The reaction is believed to proceed by initial dehydrogenation of the primary alcohol to the aldehyde that stays coordinated to ruthenium and is not released into the reaction mixture. Addition of the amine forms the hemiaminal that undergoes dehydrogenation to the amide. A catalytic cycle is proposed with the {(IiPr)Ru(II)} species as the catalytically active components.

UI MeSH Term Description Entries

Related Publications

Johan Hygum Dam, and Gyorgyi Osztrovszky, and Lars Ulrik Nordstrøm, and Robert Madsen
December 2011, The Journal of organic chemistry,
Johan Hygum Dam, and Gyorgyi Osztrovszky, and Lars Ulrik Nordstrøm, and Robert Madsen
December 2012, Chemistry (Weinheim an der Bergstrasse, Germany),
Johan Hygum Dam, and Gyorgyi Osztrovszky, and Lars Ulrik Nordstrøm, and Robert Madsen
February 2018, Chemistry, an Asian journal,
Johan Hygum Dam, and Gyorgyi Osztrovszky, and Lars Ulrik Nordstrøm, and Robert Madsen
April 2021, Organic & biomolecular chemistry,
Johan Hygum Dam, and Gyorgyi Osztrovszky, and Lars Ulrik Nordstrøm, and Robert Madsen
October 2016, The Journal of organic chemistry,
Johan Hygum Dam, and Gyorgyi Osztrovszky, and Lars Ulrik Nordstrøm, and Robert Madsen
March 2010, The Journal of organic chemistry,
Johan Hygum Dam, and Gyorgyi Osztrovszky, and Lars Ulrik Nordstrøm, and Robert Madsen
December 2014, Dalton transactions (Cambridge, England : 2003),
Johan Hygum Dam, and Gyorgyi Osztrovszky, and Lars Ulrik Nordstrøm, and Robert Madsen
November 2015, The Journal of organic chemistry,
Johan Hygum Dam, and Gyorgyi Osztrovszky, and Lars Ulrik Nordstrøm, and Robert Madsen
September 2010, Journal of the American Chemical Society,
Johan Hygum Dam, and Gyorgyi Osztrovszky, and Lars Ulrik Nordstrøm, and Robert Madsen
August 2016, Organic letters,
Copied contents to your clipboard!