Catalysis through Temporary Intramolecularity: Mechanistic Investigations on Aldehyde-Catalyzed Cope-type Hydroamination Lead to the Discovery of a More Efficient Tethering Catalyst

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• 作者：Nicolas Guimond ; Melissa J. MacDonald ; Val茅rie Lemieux ; Andr茅 M. Beauchemin
• 刊名：The Journal of the American Chemical Society
• 出版年：2012
• 出版时间：October 10, 2012
• 年：2012
• 卷：134
• 期：40
• 页码：16571-16577
• 全文大小：505K
• 年卷期：v.134,no.40(October 10, 2012)
• ISSN：1520-5126

文摘

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 (伪-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鈥?0 mol % of paraformaldehyde proved more effective than the use of 20 mol % of 伪-benzyloxyacetaldehyde, leading to high yields of intermolecular hydroamination products within 24 h at 30 掳C.