Effect of Buffer General Acid鈭払ase Catalysis on the Stereoselectivity of Ester and Thioester H/D Exchange in D2O

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• 作者：Jerry R. Mohrig ; Nicholas J. Reiter ; Randy Kirk ; Michelle R. Zawadski ; Nathan Lamarre-Vincent
• 刊名：Journal of the American Chemical Society
• 出版年：2011
• 出版时间：April 6, 2011
• 年：2011
• 卷：133
• 期：13
• 页码：5124-5128
• 全文大小：735K
• 年卷期：v.133,no.13(April 6, 2011)
• ISSN：1520-5126

文摘

As part of a comprehensive investigation on the stereochemistry of base-catalyzed 1,2-elimination and H/D exchange reactions of carbonyl compounds, we have found that the stereoselectivity of H/D exchange of 3-hydroxybutyryl N-acetylcysteamine (3) in D₂O is strongly influenced by the presence of buffers. This buffer effect is also operative with a simple acyclic ester, ethyl 3-methoxybutanoate (7). Buffers whose general-acid components are cyclic tertiary ammonium ions are particularly effective in changing the stereoselectivity. ²H NMR analysis showed that without buffer, H/D exchange of 3 produces 81鈭?2% of the 2R*, 3R* diastereomer of 2-deuterio 3 (the anti product). In the presence of 0.33 M 3-quinuclidinone buffer, only 44% of the 2R*, 3R* diastereomer was formed. With ester 7, the stereoselectivity went from 93鈭?4% in DO^{鈭?/sup>/D₂O to 60% in the presence of buffer. Phosphate buffer, as well as others, also showed substantial effects. The results are put into the context of what is known about the mechanism of H/D exchange of esters and thioesters, and the relevance of the buffer effect on the mechanism of the enoyl鈭扖oA hydratase reaction is discussed. It is likely that hydrogen bonding in the enolate鈭抌uffer acid encounter complex is an important stereochemical determinant in producing a greater amount of the 2R*, 3S* diastereomer (the syn product). Studies that involve the protonation of enolate anions in D₂O need to include the buffer general acid in any understanding of the stereoselectivity.}