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Enzyme- and Ruthenium-Catalyzed Dynamic Kinetic Resolution of Functionalized Cyclic Allylic Alcohols
Stockholm University, Faculty of Science, Department of Organic Chemistry.
Stockholm University, Faculty of Science, Department of Organic Chemistry.
Stockholm University, Faculty of Science, Department of Organic Chemistry.
2013 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 78, no 23, 12114-12120 p.Article in journal (Refereed) Published
Abstract [en]

Enantioselective synthesis of functionalized cyclic allylic alcohols via dynamic kinetic resolution has been developed. Cyclopentadienylruthenium catalysts were used for the racemization, and lipase PS-IM or CALB was employed for the resolution. By optimization of the reaction conditions the formation of the enone byproduct was minimized, making it possible to prepare a range of optically active functionalized allylic alcohols in good yields and high ee's.

Place, publisher, year, edition, pages
2013. Vol. 78, no 23, 12114-12120 p.
National Category
Organic Chemistry
Identifiers
URN: urn:nbn:se:su:diva-98273DOI: 10.1021/jo402086zISI: 000328231600050OAI: oai:DiVA.org:su-98273DiVA: diva2:685665
Funder
Swedish Research CouncilKnut and Alice Wallenberg Foundation
Note

AuthorCount:3;

Available from: 2014-01-09 Created: 2014-01-03 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Enzyme- and Transition Metal-Catalyzed Asymmetric Transformations: Application of Enzymatic (D)KR in Enantioselective Synthesis
Open this publication in new window or tab >>Enzyme- and Transition Metal-Catalyzed Asymmetric Transformations: Application of Enzymatic (D)KR in Enantioselective Synthesis
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Dynamic kinetic resolution (DKR) is a powerful method for obtaining compounds with high optical purity. The process relies on the combination of a kinetic resolution with an in situ racemization. In this thesis, a combination of an immobilized hydrolase and a transition metal-based racemization catalyst was employed in DKR to transform racemic alcohols and amines into enantioenriched esters and amides, respectively.

In the first part the DKR of 1,2-amino alcohols with different rings sizes and N-protecting groups is described. We showed that the immobilization method used to support the lipase strongly influenced the stereoselectivity of the reaction.

The second part deals with the DKR of C3-functionalized cyclic allylic alcohols affording the corresponding allylic esters in high yields and high ee’s. The protocol was also extended to include carbohydrate derivatives, leading to inversion of a hydroxyl substituted chiral center on the carbohydrate.

The third part focuses on an improved method for obtaining benzylic primary amines. By using a novel, recyclable catalyst composed of Pd nanoparticles on amino-functionalized mesocellular foam, DKR could be performed at 50 °C. Moreover, Lipase PS was for the first time employed in the DKR of amines.

In the fourth part DKR was applied in the total synthesis of Duloxetine, a compound used in the treatment of major depressive disorder. By performing a six-step synthesis, utilizing DKR in the enantiodetermining step, Duloxetine could be isolated in an overall yield of 37% and an ee >96%.

In the final part we investigated how the enantioselectivty of reactions catalyzed by Candida Antarctica lipase B for δ-substituted alkan-2-ols are influenced by water. The results showed that the enzyme displays much higher enantioselectivity in water than in anhydrous toluene. The effect was rationalized by the creation of a water mediated hydrogen bond in the active site that helps the enzyme form enantiodiscriminating binding modes.

Place, publisher, year, edition, pages
Stockholm: Department of Organic Chemistry, Stockholm University, 2014. 78 p.
Keyword
Dynamic Kinetic Resolution, Kinetic Resolution, Enzyme Catalysis, Asymmetric Synthesis
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-108351 (URN)978-91-7649-008-2 (ISBN)
Public defence
2014-11-27, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrheniusväg 16 B, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.

Available from: 2014-11-05 Created: 2014-10-22 Last updated: 2016-04-11Bibliographically approved

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