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Development and Studies of the Processes Involved in Minor Enantiomer Recycling
KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis describes the development and rationalization of processes involved in a new methodology developed in our group, minor enantiomer recycling.

The first part of the thesis addresses mechanistic studies of one of the reactions involved in minor enantiomer recycling, dual Lewis acid-Lewis base catalyzed acetylcyanation of aldehydes. The methodology uses a combination of a chiral titanium-salen  complex with a tertiary amine as a catalytic  system  in  the enantioselective  synthesis  of  O-acylated  cyanohydrins from aldehydes and ketonitriles. Mechanistic investigations revealed that the rate-determining step in the reaction changes, depending on the nature of the aldehyde that was used. It was also concluded that cyanohydrin is coordinated to the Lewis acid in the acylation step.

The second part of the thesis deals with minor enantiomer recycling, a highly selective one-pot recycling system. In a first step the product is formed as a minor and a major enantiomer by asymmetric catalysis. Recycling of the minor enantiomer, by selective kinetic resolution, regenerates the starting material. Continuous addition of a second reagent, also involved in a coupled exergonic process, leads to an increase of both yield and enantiomeric excess. Recycling procedures for the synthesis of O-acylated and O-formylated cyanohydrins have been developed with high yield and high enantiomeric excess of the products. The study includes development of the systems, comparison to other methodologies in asymmetric catalysis, and attempts to understand the processes involved.

 

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2014. , 66 p.
Series
TRITA-CHE-Report, ISSN 1654-1081 ; 2014:53
Keyword [en]
asymmetric catalysis, biocatalysis, cyanohydrins, dual activation, Lewis acid, Lewis base, minor enantiomer recycling, recycling, titanium
National Category
Organic Chemistry
Research subject
Chemistry
Identifiers
URN: urn:nbn:se:kth:diva-156635ISBN: 978-91-7595-338-0 (print)OAI: oai:DiVA.org:kth-156635DiVA: diva2:767663
Public defence
2014-12-18, F3, Lindstedtsvägen 26, KTH, Stockholm, 13:00 (English)
Opponent
Supervisors
Note

QC 20141202

Available from: 2014-12-02 Created: 2014-12-01 Last updated: 2014-12-02Bibliographically approved
List of papers
1. Minor enantiomer recycling: Metal catalyst, organocatalyst and biocatalyst working in concert
Open this publication in new window or tab >>Minor enantiomer recycling: Metal catalyst, organocatalyst and biocatalyst working in concert
Show others...
2009 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 15, no 44, 12107-12113 p.Article in journal (Refereed) Published
Abstract [en]

 A minor enantiomer recycling one-pot procedure employing two reinforcing chiral catalysts has been developed. Continuous regeneration of the achiral starting material is effected via selective enzyme-catalyzed hydrolysis of the minor product enantiomer from Lewis acid-Lewis base catalyzed addition of acyl cyanides to prochiral aldehydes in a two-phase solvent system. The process provides O-acylated cyanohydrins in close to perfect enantioselectivities, higher than those obtained in the direct process, and in high yields. A combination of a (SS)salen Ti Lewis acid and Candida antarctica lipase B provides the products with R absolute configuration, whereas the opposite enantiomer is obtained from the (R,R)-salen Ti complex and Candida rugosa lipase.

Keyword
asymmetric catalysis, enantioselectivity, enzyme catalysis, Lewis acids, organocatalysis
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-10365 (URN)10.1002/chem.200901338 (DOI)000272109100036 ()2-s2.0-72949121762 (Scopus ID)
Note
QC 20100922. Uppdaterad från Manuskript till Artikel (20100922). Tidigare titel "Minor Enantiomer Recycling: Metal Catalyst and Biocatalyst Working in Concert".Available from: 2009-05-07 Created: 2009-05-07 Last updated: 2017-12-13Bibliographically approved
2. Minor Enantiomer Recycling-Effect of Two Reinforcing Catalysts on Product Yield and Enantiomeric Excess
Open this publication in new window or tab >>Minor Enantiomer Recycling-Effect of Two Reinforcing Catalysts on Product Yield and Enantiomeric Excess
Show others...
2010 (English)In: ChemCatChem, ISSN 1867-3880, E-ISSN 1867-3899, Vol. 2, no 6, 683-693 p.Article in journal (Refereed) Published
Abstract [en]

Kinetic modeling of a recycling procedure in which the minor product enantiomer from an enantioselective catalytic reaction is selectively retransformed to starting material by a second chiral catalyst demonstrates that the enantiomeric excess of the product is not affected by the relative amounts of the two catalysts, but that the yield increases when the amount of the catalyst for the product-forming reaction is increased. The yield, but not the enantiomeric excess, is also affected by the initial substrate concentration. The recycling process is compared to sequential processes in which either the second catalyst is added after completion of the first reaction or in which the two catalysts are added simultaneously. In the sequential processes, high enantioselectivity can be obtained at the expense of product yield, whereas under recycling conditions both high enantiomeric excess and high yield can be achieved. Experimental data from a recycling procedure providing qualitative support for results from kinetic modeling are presented.

Keyword
asymmetric catalysis, biocatalysis, enantioselectivity, kinetic modeling, metal catalyst
National Category
Organic Chemistry
Identifiers
urn:nbn:se:kth:diva-46653 (URN)10.1002/cctc.200900327 (DOI)000279479100016 ()2-s2.0-79957822367 (Scopus ID)
Funder
Swedish Research CouncilKnut and Alice Wallenberg Foundation
Note
QC 20111108Available from: 2011-11-08 Created: 2011-11-04 Last updated: 2017-12-08Bibliographically approved
3. Opposite Enantiomers from Minor Enantiomer Recycling and Dynamic Kinetic Resolution Using a Single Biocatalyst
Open this publication in new window or tab >>Opposite Enantiomers from Minor Enantiomer Recycling and Dynamic Kinetic Resolution Using a Single Biocatalyst
2011 (English)In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 20-21, 3980-3984 p.Article in journal (Refereed) Published
Abstract [en]

A one-pot recycling procedure comprising Lewis acid catalyzed enantioselective addition of acetyl cyanide to (E)-2-butenal to give the O-acetylated cyanohydrin and enzyme-catalyzed conversion of the minor product enantiomer back to (E)-2-butenal provided essentially enantiopure (2R,3E)-2-acetoxy-3-pentenenitrile in close to quantitative yield. The opposite enantiomer was obtained, albeit in lower yield and with lower enantiomeric purity than that observed from the minor enantiomer recycling, by dynamic kinetic resolution consisting of reversible addition of HCN to the aldehyde coupled to enzyme-catalyzed acetylation of the cyanohydrin.

Keyword
Aldehydes, Cyanoacetylation, Enzyme catalysis, Lewis acids, Titanium
National Category
Organic Chemistry
Identifiers
urn:nbn:se:kth:diva-40679 (URN)10.1002/ejoc.201100467 (DOI)000293440900047 ()2-s2.0-79960329627 (Scopus ID)
Funder
Swedish Research CouncilKnut and Alice Wallenberg Foundation
Note
QC 20110923Available from: 2011-09-23 Created: 2011-09-20 Last updated: 2017-12-08Bibliographically approved
4. Recycling Powered by Release of Carbon Dioxide
Open this publication in new window or tab >>Recycling Powered by Release of Carbon Dioxide
2014 (English)In: ChemCatChem, ISSN 1867-3880, E-ISSN 1867-3899, Vol. 6, no 12, 3314-3317 p.Article in journal (Refereed) Published
Abstract [en]

In a cyclic process, fed with external chemical energy generated by the transformation of a compound with high chemical potential to carbon dioxide, the undesired enantiomer from a catalytic asymmetric reaction is continuously recycled to starting reagent. This minor enantiomer recycling is characterized by gradually increasing yields and product enantiomeric ratios. The requirements for maintaining a cyclic procedure are discussed; the necessity of a coupled exergonic process is demonstrated experimentally.

Keyword
carbon dioxide, cyanoformate ester, enzymes, reaction mechanisms, titanium
National Category
Organic Chemistry
Identifiers
urn:nbn:se:kth:diva-156633 (URN)10.1002/cctc.201402765 (DOI)000345975300005 ()
Funder
Swedish Research Council, 621-2012-3391Knut and Alice Wallenberg Foundation
Note

QC 20150108

Available from: 2014-12-01 Created: 2014-12-01 Last updated: 2017-12-05Bibliographically approved
5. Dual Lewis Acid-Lewis Base Catalyzed Acetylcyanation  of Aldehydes: A Mechanistic Study
Open this publication in new window or tab >>Dual Lewis Acid-Lewis Base Catalyzed Acetylcyanation  of Aldehydes: A Mechanistic Study
(English)Manuscript (preprint) (Other academic)
National Category
Organic Chemistry
Identifiers
urn:nbn:se:kth:diva-156634 (URN)
Note

QS 2014

Available from: 2014-12-01 Created: 2014-12-01 Last updated: 2014-12-02Bibliographically approved

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