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Studies on Metalloenzymatic Dynamic Kinetic Resolutions and Iron-Catalyzed Reactions of Allenes
Stockholm University, Faculty of Science, Department of Organic Chemistry. (Jan-Erling Bäckvall Group)
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The main focus of this thesis lies in the development of new transition metal-catalyzed chemoenzymatic dynamic kinetic resolutions (DKR) of both alcohols and amines. The first part of the thesis deals with the development of new heterogeneous systems for the DKR of amines. The racemization catalysts in these different systems are all composed of palladium nanoparticles supported on either mesoporous silica or incorporated in a biocomposite that is composed of a bioactive cross-linked enzyme aggregate. 

The second part of the thesis deals with the development of a homogeneous iron catalyst in the racemization of sec-alcohols for the implementation in a chemoenzymatic DKR. Two protocols for the racemization of sec-alcohols are reported. The first one could not be combined with a chemoenzymatic kinetic resolution, although this was overcome in the second iron based protocol. 

Following the successful iron catalyzed chemoenzymatic DKR of sec-alcohols, the iron catalyst was used in the cyclization of α-allenic alcohols and N-protected amines to furnish 2,3-dihydrofurans and 2,3-dihydropyrroles, respectively. The cyclization is proceeding in a diastereoselective manner.

The last part of the thesis deals with attempts to further elucidate the mechanism of activation of a known ruthenium racemization catalyst. X-ray absorption spectroscopy using synchrotron radiation was used for this purpose.

Place, publisher, year, edition, pages
Stockholm: Department of Organic Chemistry, Stockholm University , 2018. , p. 97
Keywords [en]
Racemization, Dynamic Kinetic Resolution, Enzyme Catalysis, XAS, Asymmetric Synthesis
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
URN: urn:nbn:se:su:diva-153952ISBN: 978-91-7797-195-5 (print)ISBN: 978-91-7797-196-2 (electronic)OAI: oai:DiVA.org:su-153952DiVA, id: diva2:1189384
Public defence
2018-04-27, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Manuscript. Paper 7: Manuscript. Paper 8: Manuscript.

Available from: 2018-04-04 Created: 2018-03-09 Last updated: 2018-03-22Bibliographically approved
List of papers
1. Chemoenzymatic Dynamic Kinetic Resolution of Primary Amines Using a Recyclable Palladium Nanoparticle Catalyst Together with Lipases
Open this publication in new window or tab >>Chemoenzymatic Dynamic Kinetic Resolution of Primary Amines Using a Recyclable Palladium Nanoparticle Catalyst Together with Lipases
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2014 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 79, no 9, p. 3747-3751Article 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.

National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-104395 (URN)10.1021/jo500508p (DOI)000335490700002 ()
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: 2018-03-20Bibliographically approved
2. Co-immobilization of an Enzyme and a Metal into the Compartments of Mesoporous Silica for Cooperative Tandem Catalysis: An Artificial Metalloenzyme
Open this publication in new window or tab >>Co-immobilization of an Enzyme and a Metal into the Compartments of Mesoporous Silica for Cooperative Tandem Catalysis: An Artificial Metalloenzyme
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2013 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 52, no 52, p. 14006-14010Article in journal (Refereed) Published
Abstract [en]

Surpassing nature: A hybrid catalyst in which Candida antarctica lipase B and a nanopalladium species are co-immobilized into the compartments of mesoporous silica is presented. The metal nanoparticles and the enzyme are in close proximity to one another in the cavities of the support. The catalyst mimics a metalloenzyme and was used for dynamic kinetic resolution of a primary amine in high yield and excellent enantioselectivity.

Keywords
artificial deracemase, biocatalysis, dynamic kinetic resolution, hybrid catalysts, metal catalysis
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-96701 (URN)10.1002/anie.201306487 (DOI)000328531100019 ()
Funder
Swedish Research CouncilKnut and Alice Wallenberg Foundation
Note

AuthorCount: 7;

Available from: 2013-11-25 Created: 2013-11-25 Last updated: 2018-03-20Bibliographically approved
3. Design of a Pd(0)-CalB CLEA Biohybrid Catalyst and Its Application in a One-Pot Cascade Reaction
Open this publication in new window or tab >>Design of a Pd(0)-CalB CLEA Biohybrid Catalyst and Its Application in a One-Pot Cascade Reaction
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2017 (English)In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 7, no 3, p. 1601-1605Article in journal (Refereed) Published
Abstract [en]

Herein, a design of a biohybrid catalyst is described, consisting of Pd nanoparticles and a cross-linked network of aggregated lipase B enzyme of Candida antarctica (CalB CLEA) functioning as an active support for the Pd nanoparticles. Both entities of the hybrid catalyst showed good catalytic activity. The applicability was demonstrated in a one-pot reaction, where the Pd-catalyzed cycloisomerization of 4-pentynoic acid afforded a lactone that serves as an acyl donor in a subsequent selective enzymatic kinetic resolution of a set of sec-alcohols. The catalyst proved to be robust and could be recycled five times without a significant loss of activity.

Keywords
kinetic resolution, biohybrid catalyst, Pd nanoparticles, CalB, cycloisomerization, one-pot cascade reaction
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-142484 (URN)10.1021/acscatal.6b03481 (DOI)000395726500011 ()
Available from: 2017-05-16 Created: 2017-05-16 Last updated: 2018-03-09Bibliographically approved
4. Application and further structure elucidation of Pd(0)-CalB CLEA biohybrid catalyst- Chemoenzymatic dynamic kinetic resolution of primary benzylic amines
Open this publication in new window or tab >>Application and further structure elucidation of Pd(0)-CalB CLEA biohybrid catalyst- Chemoenzymatic dynamic kinetic resolution of primary benzylic amines
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(English)Manuscript (preprint) (Other academic)
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-153897 (URN)
Available from: 2018-03-07 Created: 2018-03-07 Last updated: 2018-03-20Bibliographically approved
5. Evaluation of Fe and Ru Pincer-Type Complexes as Catalysts for the Racemization of Secondary Benzylic Alcohols
Open this publication in new window or tab >>Evaluation of Fe and Ru Pincer-Type Complexes as Catalysts for the Racemization of Secondary Benzylic Alcohols
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2016 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 22, no 33, p. 11583-11586Article in journal (Refereed) Published
Abstract [en]

Fe and Ru pincer-type catalysts are used for the racemization of benzylic alcohols. Racemization with the Fe catalyst was achieved within 30 minutes under mild reaction conditions, with a catalyst loading as low as 2 mol %. This reaction constitutes the first example of an iron-catalyzed racemization of an alcohol. The efficiency for racemization of the Fe catalyst and its Ru analogue was evaluated for a wide range of sec-benzylic alcohols. The commercially available Ru complex proved to be highly robust and even tolerated the presence of water in the reaction mixture.

Keywords
iron, pincer ligands, racemization, ruthenium, secondary alcohols
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-135116 (URN)10.1002/chem.201601793 (DOI)000382921600015 ()27311070 (PubMedID)
Available from: 2016-11-03 Created: 2016-10-31 Last updated: 2018-03-20Bibliographically approved
6. Chemoenzymatic Dynamic Kinetic Resolution of Secondary Alcohols Using an Air- and Moisture-Stable Iron Racemization Catalyst
Open this publication in new window or tab >>Chemoenzymatic Dynamic Kinetic Resolution of Secondary Alcohols Using an Air- and Moisture-Stable Iron Racemization Catalyst
2017 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 23, no 5, p. 1048-1051Article in journal (Refereed) Published
Abstract [en]

Herein, we report on a metalloenzymatic dynamic kinetic resolution of sec-alcohols employing an iron-based racemization catalyst together with a lipase. The iron catalyst was evaluated in racemization and then used in dynamic kinetic resolution of a number of sec-alcohols to give enantiomerically pure products in good to high yields. The iron catalyst is air and moisture stable and is readily accessible.

Keywords
dynamic kinetic resolution, enzyme catalysis, iron catalysis, racemization, secondary alcohols
National Category
Chemical Sciences
Identifiers
urn:nbn:se:su:diva-141286 (URN)10.1002/chem.201605754 (DOI)000395753000014 ()28005307 (PubMedID)
Available from: 2017-04-04 Created: 2017-04-04 Last updated: 2018-03-09Bibliographically approved
7. Efficient Formation of 2,3-Dihydrofurans via Iron-Catalyzed Cycloisomerization of alpha-Allenols
Open this publication in new window or tab >>Efficient Formation of 2,3-Dihydrofurans via Iron-Catalyzed Cycloisomerization of alpha-Allenols
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2018 (English)In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 8, no 1, p. 12-16Article in journal (Refereed) Published
Abstract [en]

Herein, we report a highly efficient iron-catalyzed intramolecular nucleophilic cyclization of alpha-allenols to furnish substituted 2,3-dihydrofurans under mild reaction conditions. A highly diastereoselective variant of the reaction was developed as well, giving diastereomeric ratios of up to 98:2. The combination of the iron-catalyzed cycloisomerization with enzymatic resolution afforded the 2,3-dihydrofuran in high ee. A detailed DFT study provides insight into the reaction mechanism and gives a rationalization for the high chemo-and diastereoselectivity.

Keywords
iron catalysis, alpha-allenols, diastereoselective, 2, 3-dihydrofurans, homogeneous
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-152566 (URN)10.1021/acscatal.7b03515 (DOI)000419751100003 ()
Available from: 2018-02-19 Created: 2018-02-19 Last updated: 2018-03-20Bibliographically approved
8. Iron Catalyzed Cyclization of N-protected a-Allenic Amines to 2,3-dihydropyrroles
Open this publication in new window or tab >>Iron Catalyzed Cyclization of N-protected a-Allenic Amines to 2,3-dihydropyrroles
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(English)Manuscript (preprint) (Other academic)
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-153948 (URN)
Available from: 2018-03-09 Created: 2018-03-09 Last updated: 2018-03-20Bibliographically approved
9. In-Situ Structure Determination of a Ruthenium Racemization Catalyst and its Activated Intermediates using X-ray Absorption Spectroscopy
Open this publication in new window or tab >>In-Situ Structure Determination of a Ruthenium Racemization Catalyst and its Activated Intermediates using X-ray Absorption Spectroscopy
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(English)Manuscript (preprint) (Other academic)
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-153950 (URN)
Available from: 2018-03-09 Created: 2018-03-09 Last updated: 2018-03-20Bibliographically approved

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