1349708-34-4Relevant academic research and scientific papers
Catalysis through temporary intramolecularity: Mechanistic investigations on aldehyde-catalyzed cope-type hydroamination lead to the discovery of a more efficient tethering catalyst
Guimond, Nicolas,MacDonald, Melissa J.,Lemieux, Valerie,Beauchemin, Andre M.
, p. 16571 - 16577,7 (2020/09/15)
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.
A catalytic tethering strategy: Simple aldehydes catalyze intermolecular alkene hydroaminations
MacDonald, Melissa J.,Schipper, Derek J.,Ng, Peter J.,Moran, Joseph,Beauchemin, Andre M.
supporting information; experimental part, p. 20100 - 20103 (2012/02/01)
Herein we describe a catalytic tethering strategy in which simple aldehyde precatalysts enable, through temporary intramolecularity, room-temperature intermolecular hydroamination reactivity and the synthesis of vicinal diamines. The catalyst allows the formation of a mixed aminal from an allylic amine and a hydroxylamine, resulting in a facile intramolecular hydroamination event. The promising enantioselectivities obtained with a chiral aldehyde also highlight the potential of this catalytic tethering approach in asymmetric catalysis and demonstrate that efficient enantioinduction relying only on temporary intramolecularity is possible.
