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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
Author(s) -
Hayashi Yujiro,
Kawamoto Yuya,
Honda Masaki,
Okamura Daichi,
Umemiya Shigenobu,
Noguchi Yuka,
Mukaiyama Takasuke,
Sato Itaru
Publication year - 2014
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201403588
Subject(s) - nitromethane , nitroethane , stereocenter , michael reaction , chemistry , silylation , nitroaldol reaction , organic chemistry , isomerization , reactivity (psychology) , addition reaction , catalysis , quaternary carbon , silyl enol ether , medicinal chemistry , enantioselective synthesis , medicine , alternative medicine , pathology
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.