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Chemoenzymatic Dynamic Kinetic Resolution of Primary Amines Using a Recyclable Palladium Nanoparticle Catalyst Together with Lipases
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.
Stockholm University, Faculty of Science, Department of Organic Chemistry.
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2014 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 79, no 9, 3747-3751 p.Article in journal (Refereed) Published
Abstract [en]

A catalyst consisting of palladium nanoparticles supported on amino-functionalized siliceous mesocellular foam (Pd-AmP-MCF) was used in chemoenzymatic dynamic kinetic resolution (DKR) to convert primary amines to amides in high yields and excellent ee's. The efficiency of the nanocatalyst at temperatures below 70 degrees C enables reaction conditions that are more suitable for enzymes. In the present study, this is exemplified by subjecting 1-phenylethylamine (1a) and analogous benzylic amines to DKR reactions using two commercially available lipases, Novozyme-435 (Candida antartica Lipase B) and Amano Lipase PS-C1 (lipase from Burkholderia cepacia) as biocatalysts. The latter enzyme has not previously been used in the DKR of amines because of its low stability at temperatures over 60 degrees C. The viability of the heterogeneous Pd-AmP-MCF was further demonstrated in a recycling study, which shows that the catalyst can be reused up to five times.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2014. Vol. 79, no 9, 3747-3751 p.
National Category
Organic Chemistry
Identifiers
URN: urn:nbn:se:su:diva-104395DOI: 10.1021/jo500508pISI: 000335490700002OAI: oai:DiVA.org:su-104395DiVA: diva2:724328
Funder
Berzelii Centre EXSELENTEU, European Research CouncilKnut and Alice Wallenberg FoundationSwedish Research Council
Note

AuthorCount:5;

Available from: 2014-06-12 Created: 2014-06-10 Last updated: 2017-12-05Bibliographically 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)
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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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