Catalytic Enantioselective Conjugate Addition of Carbamates
Claudio Palomo,* Mikel Oiarbide, Rajkumar Halder, Michael Kelso, Enrique Gómez-Bengoa and Jesús M. García
*Departamento de Química Orgánica I, Facultad de Química, Universidad del
País Vasco, Apdo. 1072, 20080 San Sebastián, Spain,
Email: claudio.palomo
ehu.es
C. Palomo, M. Oiarbide, R. Halder, M. Kelso, E. Gómez-Bengoa, J. M. García, J. Am. Chem. Soc., 2004, 126, 9188-9189.
DOI: 10.1021/ja047004e
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Abstract
A catalytic, asymmetric conjugate addition of carbamates to enoyl systems provides a highly enantioselective two-step access to N-protected β-amino acids.
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Details
The document discusses the first highly enantioselective conjugate addition reactions of carbamates to enones catalyzed by chiral Lewis acids, specifically bis(oxazoline)-copper complexes. This method addresses the challenge of alternative nonselective pathways catalyzed by Brønsted acids. The researchers hypothesized that using chelating α-hydroxy enones could preferentially coordinate to oxophilic metal centers, minimizing these pathways. Initial screenings showed that catalyst 9 (Cu(OTf)2) was highly effective, yielding the desired product with 96% enantiomeric excess (ee). Further experiments demonstrated that various β-alkyl-substituted R′-hydroxy enones reacted well with different carbamates, consistently producing high yields and excellent enantioselectivities. The study also highlighted the practical importance of these reactions in synthesizing optically pure N-protected β-amino acids, which are valuable in pharmaceuticals and biostable peptidomimetics. The research was supported by the University of the Basque Country and the Spanish Ministry of Science and Technology. The findings open new avenues for expanding this catalytic system to other asymmetric reactions.
Key Words
β-Amino Ketones, β-Amino Acids, Oxidative Cleavage, Sodium Periodat
ID: J48-Y2004-1610
