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Combined ruthenium(II)- and lipase catalysis for efficient dynamic kinetic resolution of sec-alcohols. Insight into a new racemization mechanism
Stockholm University, Faculty of Science, Department of Organic Chemistry.
Stockholm University, Faculty of Science, Department of Organic Chemistry.
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2005 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 127, no 24, 8817-8825 p.Article in journal (Refereed) Published
Abstract [en]


Pentaphenylcyclopentadienyl ruthenium complexes (3) are excellent catalysts for the racemization of secondary alcohols at ambient temperature. The combination of this process with enzymatic resolution of the alcohols results in a highly efficient synthesis of enantiomerically pure acetates at room temperature with short reaction times for most substrates. This new reaction was applied to a wide range of functionalized alcohols including heteroaromatic alcohols, and for many of the latter, enantiopure acetates were efficiently prepared for the first time via dynamic kinetic resolution (DKR). Different substituted cyclopentadienyl ruthenium complexes were prepared and studied as catalysts for racemization of alcohols. Pentaaryl-substituted cyclopentadienyl complexes were found to be highly efficient catalysts for the racemization. Substitution of one of the aryl groups by an alkyl group considerably slows down the racemization process. A study of the racemization of (S)-1-phenylethanol catalyzed by ruthenium hydride η5-Ph5CpRu(CO)2H (8) indicates that the racemization takes place within the coordination sphere of the ruthenium catalyst. This conclusion was supported by the lack of ketone exchange in the racemization of (S)-1-phenylethanol performed in the presence of p-tolyl methyl ketone (1 equiv), which gave <1% of 1-(p-tolyl)ethanol. The structures of ruthenium chloride and iodide complexes 3a and 3c and of ruthenium hydride complex 8 were confirmed by X-ray analysis.

Place, publisher, year, edition, pages
American Chemical Society , 2005. Vol. 127, no 24, 8817-8825 p.
National Category
Organic Chemistry
URN: urn:nbn:se:su:diva-23891DOI: 10.1021/ja051576xOAI: diva2:195179
Part of urn:nbn:se:su:diva-537Available from: 2005-05-13 Created: 2005-05-13 Last updated: 2010-12-08Bibliographically approved
In thesis
1. Ruthenium-catalyzed redox reactions and lipase-catalyzed asymmetric transformations of alcohols
Open this publication in new window or tab >>Ruthenium-catalyzed redox reactions and lipase-catalyzed asymmetric transformations of alcohols
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The major part of this thesis describes the synthesis of enantiopure alcohols and diols by combining ruthenium-catalyzed redox reactions that lead to racemization or epimerization and lipase-catalyzed asymmetric trans-formations in one-pot.

A mechanistic study of the unexpected facile formation of meso-diacetate products found in enzyme-catalyzed acetylations of alkanediols with Candida antarctica lipase B (CALB) was first performed. By deuterium labeling it was found that the formation of meso-diacetates proceeds via different mechanisms for 2,4-pentanediol and 2,5-hexanediol. Whereas the first reacts via an intramolecular acyl migration, the latter proceeds via a direct, anomalous S-acylation of the alcohol. The acyl migration occurring in the 2,4-pentanediol monoacetate was taken advantage of in asymmetric transformations of substituted 1,3-diols by combining it with a ruthenium-catalyzed epimerization and an enzymatic transesterification using CALB. The in situ coupling of these three processes results in de-epimerization and deracemization of acyclic, unsymmetrical 1,3-diols and constitutes a novel dynamic kinetic asymmetric transformation (DYKAT) concept.

Racemization of secondary alcohols effected by a new ruthenium complex was combined in one-pot with an enzyme-catalyzed transesterification, leading to a chemoenzymatic dynamic kinetic resolution (DKR) operating at room temperature. Aromatic, aliphatic, heterocyclic and functionalized alcohols were subjected to the procedure. A mechanism for racemization by this ruthenium complex has been proposed and experimental indications for hydrogen transfer within the coordination sphere of ruthenium were found. The same ruthenium catalyst was used for epimerization in DYKAT of 1,2-diols, and a very similar complex was employed in isomerization of allylic alcohols to saturated ketones. The former method is a substrate extension of the above principle applied for DYKAT of 1,3-diols. The combination of a lipase and an organocatalyst was demonstrated by linking a lipase-catalyzed transesterification to a proline-mediated aldol reaction for the production of enantiopure (S)-β-hydroxy ketones and acetylated (R)-aldols.

Place, publisher, year, edition, pages
Stockholm: Institutionen för organisk kemi, 2005
ruthenium, lipase, catalysis, alcohols, diols
National Category
Chemical Sciences
urn:nbn:se:su:diva-537 (URN)91-7155-053-4 (ISBN)
Public defence
2005-06-10, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 12 A, Stockholm, 16:15
Available from: 2005-05-13 Created: 2005-05-13Bibliographically approved

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Martín-Matute, BelénBäckvall, Jan-E.
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