title: Catalysis through temporary intramolecularity: mechanistic investigations on aldehyde-catalyzed Cope-type hydroamination lead to the discovery of a more efficient tethering catalyst.
abstract: Mechanistic investigations on the aldehyde-catalyzed intermolecular hydroamination of allylic amines using N-alkylhydroxylamines are presented. Under the reaction conditions, the presence of a specific aldehyde catalyst allows formation of a mixed aminal intermediate, which permits intramolecular Cope-type hydroamination. The reaction was determined to be first-order in both the aldehyde catalyst (α-benzyloxyacetaldehyde) and the allylic amine. However, the reaction displays an inverse order behavior in benzylhydroxylamine, which reveals a significant off-cycle pathway and highlights the importance of an aldehyde catalyst that promotes a reversible aminal formation. Kinetic isotope effect experiments suggest that hydroamination is the rate-limiting step of this catalytic cycle. Overall, these results enabled the elaboration of a more accurate catalytic cycle and led to the development of a more efficient catalytic system for alkene hydroamination. The use of 5-10 mol % of paraformaldehyde proved more effective than the use of 20 mol % of α-benzyloxyacetaldehyde, leading to high yields of intermolecular hydroamination products within 24 h at 30 °C.
authors.affiliation: Centre for Catalysis Research and Innovation, Department of Chemistry, University of Ottawa, 10 Marie-Curie, Ottawa, Ontario K1N 6N5, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Guimond
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: MacDonald
authors.forename: Valérie
authors.initials: V
authors.lastname: Lemieux
authors.forename: André M
authors.initials: AM
authors.lastname: Beauchemin
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D000498:Allyl Compounds / Q000737:chemistry*; D000586:Amination; D000588:Amines / Q000737:chemistry; D002384:Catalysis; D006898:Hydroxylamines / Q000737:chemistry*
chemical_list: D000447:Aldehydes; D000498:Allyl Compounds; D000588:Amines; D006898:Hydroxylamines