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Ruthenium-catalyzed redox reactions and lipase-catalyzed asymmetric transformations of alcohols
Stockholm University, Faculty of Science, Department of Organic Chemistry.
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.
Keyword [en]
ruthenium, lipase, catalysis, alcohols, diols
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:su:diva-537ISBN: 91-7155-053-4 (print)OAI: oai:DiVA.org:su-537DiVA: diva2:195182
Public defence
2005-06-10, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 12 A, Stockholm, 16:15
Opponent
Supervisors
Available from: 2005-05-13 Created: 2005-05-13Bibliographically approved
List of papers
1. On the mechanism of the unexpected facile formation of meso-diacetate products in enzymatic acetylation of alkanediols
Open this publication in new window or tab >>On the mechanism of the unexpected facile formation of meso-diacetate products in enzymatic acetylation of alkanediols
2003 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 68, 2216-2222 p.Article in journal (Refereed) Published
National Category
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-23887 (URN)10.1021/jo026652i (DOI)
Note

Part of urn:nbn:se:su:diva-537

Available from: 2005-05-13 Created: 2005-05-13 Last updated: 2017-12-13Bibliographically approved
2. One-pot synthesis of enantiopure syn-1,3-diacetates from racemic diastereomeric mixtures of 1,3-diols by dynamic kinetic asymmetric transformation
Open this publication in new window or tab >>One-pot synthesis of enantiopure syn-1,3-diacetates from racemic diastereomeric mixtures of 1,3-diols by dynamic kinetic asymmetric transformation
2004 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 101, 5761-5766 p.Article in journal (Refereed) Published
National Category
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-23888 (URN)
Note

Part of urn:nbn:se:su:diva-537

Available from: 2005-05-13 Created: 2005-05-13 Last updated: 2017-12-13Bibliographically approved
3. Tandem enantioselective organo- and biocatalysis: a direct entry for the synthesis of enantiomerically pure aldols
Open this publication in new window or tab >>Tandem enantioselective organo- and biocatalysis: a direct entry for the synthesis of enantiomerically pure aldols
2004 (English)In: Tetrahedron Letters, ISSN 0040-4039, E-ISSN 1359-8562, Vol. 45, 7697-7701 p.Article in journal (Refereed) Published
National Category
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-23889 (URN)
Note

Part of urn:nbn:se:su:diva-537

Available from: 2005-05-13 Created: 2005-05-13 Last updated: 2017-12-13Bibliographically approved
4. Highly compatible metal and enzyme catalysts for efficient dynamic kinetic resolution of alcohols at ambient temperature
Open this publication in new window or tab >>Highly compatible metal and enzyme catalysts for efficient dynamic kinetic resolution of alcohols at ambient temperature
2004 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 43, 6535-6539 p.Article in journal (Refereed) Published
National Category
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-23890 (URN)
Note

Part of urn:nbn:se:su:diva-537

Available from: 2005-05-13 Created: 2005-05-13 Last updated: 2017-12-13Bibliographically approved
5. Combined ruthenium(II)- and lipase catalysis for efficient dynamic kinetic resolution of sec-alcohols. Insight into a new racemization mechanism
Open this publication in new window or tab >>Combined ruthenium(II)- and lipase catalysis for efficient dynamic kinetic resolution of sec-alcohols. Insight into a new racemization mechanism
Show others...
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
National Category
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-23891 (URN)10.1021/ja051576x (DOI)
Note
Part of urn:nbn:se:su:diva-537Available from: 2005-05-13 Created: 2005-05-13 Last updated: 2017-12-13Bibliographically approved
6. Dynamic kinetic asymmetric transformation of 1,2-diols: an enantioselective synthesis of syn-1,2-diacetates
Open this publication in new window or tab >>Dynamic kinetic asymmetric transformation of 1,2-diols: an enantioselective synthesis of syn-1,2-diacetates
Manuscript (Other academic)
Identifiers
urn:nbn:se:su:diva-23892 (URN)
Note
Part of urn:nbn:se:su:diva-537Available from: 2005-05-13 Created: 2005-05-13 Last updated: 2010-01-13Bibliographically approved
7. Highly efficient redox isomerization of allylic alcohols at ambient temperature catalyzed by novel ruthenium cyclopentadienyl complexes: New insight into the mechanism
Open this publication in new window or tab >>Highly efficient redox isomerization of allylic alcohols at ambient temperature catalyzed by novel ruthenium cyclopentadienyl complexes: New insight into the mechanism
Show others...
2005 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 11, no 20, 5832-5842 p.Article in journal (Refereed) Published
Abstract [en]

A range of ruthenium cyclopentadienyl (Cp) complexes have been prepared and used for isomerization of allylic alcohols to the corresponding saturated carbonyl compounds. Complexes bearing CO ligands show higher activity than those with PPh3 ligands. The isomerization rate is highly affected by the substituents on the Cp ring. Tetra(phenyl)methyl-substituted catalysts rapidly isomerize allylic alcohols under very mild reaction conditions (ambient temperature) with short reaction times. Substituted allylic alcohols have been isomerized by employing Ru–Cp complexes. A study of the isomerization catalyzed by [Ru(Ph5Cp)(CO)2H] (14) indicates that the isomerization catalyzed by ruthenium hydrides partly follows a different mechanism than that of ruthenium halides activated by KOtBu. Furthermore, the lack of ketone exchange when the isomerization was performed in the presence of an unsaturated ketone (1 equiv), different from that obtained by dehydrogenation of the starting allylic alcohol, supports a mechanism in which the isomerization takes place within the coordination sphere of the ruthenium catalyst.

Place, publisher, year, edition, pages
Wiley, 2005
Keyword
allylic compounds;hydrides;isomerization;mechanism elucidation;ruthenium
National Category
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-23893 (URN)10.1002/chem.200500490 (DOI)
Note
Part of urn:nbn:se:su:diva-537Available from: 2005-05-13 Created: 2005-05-13 Last updated: 2017-12-13Bibliographically approved

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