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Updated: Jun 12, 2025

A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
Published on: February 16, 2020
New Entries in Organocatalysts from an Alkaloid Library; Development of Aminal Catalysis for a Michael Reaction Based
Kyosuke Yamanishi1, Gin Ashihara1, Shinya Shiomi1
1Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
Abstract:
Natural products have historically been actively evaluated for their biological activity in the development of pharmaceuticals, while their evaluation as asymmetric catalysts has rarely been explored. In this study, we evaluated the catalytic activity of the natural product library. Three naturally occurring alkaloids, gardnerine, spiradine A, and calycanthine, were found to catalyze an asymmetric Michael reaction using oxindole and nitrostyrene. We further studied (+)-calycanthine, which is characterized by its aminal structure. Concise synthetic and extraction protocols were developed to provide both enantiomers of calycanthine. Further derivatization of this alkaloid led to improved enantioselectivity in a model reaction. Computational studies suggested that the aminal moiety of the catalyst activated nucleophiles and electrophiles through multiple hydrogen bonding interactions, including nonclassical hydrogen bonds between carboxylic acid and the aminal C-H.
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