Diphenylprolinol Silyl Ether Catalyzed Asymmetric Michael Reaction of Nitroalkanes and β,β‐Disubstituted α,β‐Unsaturated Aldehydes for the Construction of All‐Carbon Quaternary Stereogenic Centers |
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Authors: | Prof?Dr Yujiro Hayashi Yuya Kawamoto Masaki Honda Daichi Okamura Shigenobu Umemiya Yuka Noguchi Takasuke Mukaiyama Prof?Dr Itaru Sato |
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Institution: | Department of Chemistry, Graduate School of Science, Tohoku University, 6–3 Aramaki‐Aza Aoba, Aoba‐ku, Sendai 980‐8578 (Japan) |
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Abstract: | The asymmetric Michael reaction of nitroalkanes and β,β‐disubstituted α,β‐unsaturated aldehydes was catalyzed by diphenylprolinol silyl ether to afford 1,4‐addition products with an all‐carbon quaternary stereogenic center with excellent enantioselectivity. The reaction is general for β‐substituents such as β‐aryl and β‐alkyl groups, and both nitromethane and nitroethane can be employed. The addition of nitroethane is considered a synthetic equivalent of the asymmetric Michael reaction of ethyl and acetyl substituents by means of radical denitration and Nef reaction, respectively. The short asymmetric synthesis of (S)‐ethosuximide with a quaternary carbon center was accomplished by using the present asymmetric Michael reaction as the key step. The reaction mechanism that involves the E/Z isomerization of α,β‐unsaturated aldehydes, the retro‐Michael reaction, and the different reactivity between nitromethane and nitroethane is discussed. |
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Keywords: | asymmetric synthesis enantioselectivity isomerization Michael addition organocatalysis |
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