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Asymmetric organocatalytic direct aldol reactions of ketones with alpha-keto acids and their application to the synthesis of 2-hydroxy-gamma-butyrolactones.
J Org Chem. 2007 Dec 21; 72(26):9905-13.JO

Abstract

A variety of organocatalysts for the asymmetric direct aldol reactions of ketones with alpha-keto acids were designed on the basis of molecular recognition and prepared from proline and aminopyridines. The organic molecule 8e, derived from proline and 6-methyl-2-amino pyridine, was the best catalyst, affording excellent enantioselectivities (up to 98% ee) for the direct aldol reactions of acetone or 2-butanone with a wide range of alpha-keto acids and for the reactions of various acyclic aliphatic ketones with 3-(2-nitrophenyl)-2-oxopropanoic acid. The aldol adducts could be converted to 2-hydroxy-gamma-butyrolactones by reaction sequences of diastereoselective reduction and lactonization. Experimental and theoretical studies on the transition states revealed that the amide N-H and the pyridine N of the organocatalyst selectively form hydrogen bonds with the keto oxygen and the carboxylic acid hydroxy of the alpha-keto acid, respectively. These two hydrogen-bonding interactions are important for the reactivity and enantioselectivity of the direct asymmetric aldol condensation.

Authors+Show Affiliations

Xu XY
Hefei National Laboratory for Physical Sciences at Microscale and Department of Chemistry, University of Science and Technology of China, Hefei 230026, China.
Tang Z
No affiliation info available
Wang YZ
No affiliation info available
Luo SW
No affiliation info available
Cun LF
No affiliation info available
Gong LZ
No affiliation info available

MeSH

4-ButyrolactoneAminopyridinesButanonesCatalysisKeto AcidsKetonesModels, MolecularMolecular StructureProlineStereoisomerism

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18004868

Citation

Xu, Xiao-Ying, et al. "Asymmetric Organocatalytic Direct Aldol Reactions of Ketones With Alpha-keto Acids and Their Application to the Synthesis of 2-hydroxy-gamma-butyrolactones." The Journal of Organic Chemistry, vol. 72, no. 26, 2007, pp. 9905-13.
Xu XY, Tang Z, Wang YZ, et al. Asymmetric organocatalytic direct aldol reactions of ketones with alpha-keto acids and their application to the synthesis of 2-hydroxy-gamma-butyrolactones. J Org Chem. 2007;72(26):9905-13.
Xu, X. Y., Tang, Z., Wang, Y. Z., Luo, S. W., Cun, L. F., & Gong, L. Z. (2007). Asymmetric organocatalytic direct aldol reactions of ketones with alpha-keto acids and their application to the synthesis of 2-hydroxy-gamma-butyrolactones. The Journal of Organic Chemistry, 72(26), 9905-13.
Xu XY, et al. Asymmetric Organocatalytic Direct Aldol Reactions of Ketones With Alpha-keto Acids and Their Application to the Synthesis of 2-hydroxy-gamma-butyrolactones. J Org Chem. 2007 Dec 21;72(26):9905-13. PubMed PMID: 18004868.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Asymmetric organocatalytic direct aldol reactions of ketones with alpha-keto acids and their application to the synthesis of 2-hydroxy-gamma-butyrolactones. AU - Xu,Xiao-Ying, AU - Tang,Zhuo, AU - Wang,Yan-Zhao, AU - Luo,Shi-Wei, AU - Cun,Lin-Feng, AU - Gong,Liu-Zhu, Y1 - 2007/11/16/ PY - 2007/11/17/pubmed PY - 2008/3/26/medline PY - 2007/11/17/entrez SP - 9905 EP - 13 JF - The Journal of organic chemistry JO - J Org Chem VL - 72 IS - 26 N2 - A variety of organocatalysts for the asymmetric direct aldol reactions of ketones with alpha-keto acids were designed on the basis of molecular recognition and prepared from proline and aminopyridines. The organic molecule 8e, derived from proline and 6-methyl-2-amino pyridine, was the best catalyst, affording excellent enantioselectivities (up to 98% ee) for the direct aldol reactions of acetone or 2-butanone with a wide range of alpha-keto acids and for the reactions of various acyclic aliphatic ketones with 3-(2-nitrophenyl)-2-oxopropanoic acid. The aldol adducts could be converted to 2-hydroxy-gamma-butyrolactones by reaction sequences of diastereoselective reduction and lactonization. Experimental and theoretical studies on the transition states revealed that the amide N-H and the pyridine N of the organocatalyst selectively form hydrogen bonds with the keto oxygen and the carboxylic acid hydroxy of the alpha-keto acid, respectively. These two hydrogen-bonding interactions are important for the reactivity and enantioselectivity of the direct asymmetric aldol condensation. SN - 0022-3263 UR - https://www.unboundmedicine.com/medline/citation/18004868/Asymmetric_organocatalytic_direct_aldol_reactions_of_ketones_with_alpha_keto_acids_and_their_application_to_the_synthesis_of_2_hydroxy_gamma_butyrolactones_ DB - PRIME DP - Unbound Medicine ER -