Enantio- and Diastereoselective Michael Reaction of 1,3-Dicarbonyl Compounds to Nitroolefins Catalyzed by a Bifunctional Thiourea
Tomotaka Okino, Yasutaka Hoashi, Tomihiro Furukawa, Xuenong Xu and Yoshiji Takemoto*
*Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida,
Sakyo-ku, Kyoto 606-8501, Japan, Email: takemotopharm.kyoto-u.ac.jp
T. Okino, Y. Hoashi, T. Fukukawa, X. Xu, Y. Takemoto, J. Am. Chem. Soc., 2005, 127, 119-125.
DOI: 10.1021/ja044370p
Abstract
A new bifunctional catalyst bearing a thiourea moiety and an amino group was highly efficient for the asymmetric Michael reaction of 1,3-dicarbonyl compounds to nitroolefins to afford the Michael adducts with high enantio- and diastereoselectivity.
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Details
The document discusses the development and application of novel bifunctional organocatalysts containing a thiourea moiety and an amino group for enantio- and diastereoselective Michael reactions of 1,3-dicarbonyl compounds to nitroolefins. The research, conducted by Tomotaka Okino and colleagues at Kyoto University, highlights the synthesis of various thiourea derivatives and their evaluation in Michael reactions. Among these, thiourea 1e, featuring 3,5-bis(trifluoromethyl)benzene and dimethylamino groups, demonstrated high efficiency and selectivity, achieving up to 93% enantiomeric excess (ee). The study also explores the reaction mechanism, suggesting that the thiourea and amino groups activate the nitroolefin and 1,3-dicarbonyl compound, respectively, facilitating the formation of the Michael adduct. The catalysts were further applied to synthesize (R)-(-)-baclofen, a drug used for treating neuromuscular conditions, with high enantioselectivity. The research provides insights into the structure-activity relationship of these catalysts and proposes a reaction mechanism based on kinetic studies. The findings offer a significant advancement in the field of asymmetric catalysis, enabling the efficient synthesis of complex molecules with high stereoselectivity.
Key Words
Michael Addition, Organocatalysis, Nitro Compounds
ID: J48-Y2005-2120