New Methods for Chiral Cyanohydrin Synthesis
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
This thesis deals with method development in asymmetric catalysis and specifically syntheses of enantioenriched O-functionalized cyanohydrins.
The first part describes the development of a method for the synthesis of O‑alkoxycarbonylated and O-acylated cyanohydrins. Ethyl cyanoformate and acyl cyanides were added to aldehydes in a reaction catalyzed by a chiral dimeric Ti-salen complex together with a tertiary amine. High yields and enantioselectivities were in most cases obtained. Mechanistic studies were performed and a reaction mechanism was proposed.
The second part describes a method in which the undesired minor enantiomer in a Lewis acid–Lewis base-catalyzed acylcyanation is continuously recycled into prochiral starting material. Close to enantiopure O‑acylated cyanohydrins were obtained in high yields.
The third part deals with asymmetric acylcyanations of ketones. Acetyl cyanide was found to add to α‑ketoesters in a reaction catalyzed by a chiral Lewis base. Yields up to 77% and 82% ee were obtained.
The final part describes an enzymatic method for high-throughput analysis of O‑acylated cyanohydrins. The enantiomeric excess and conversion were determined for products obtained from a number of aromatic and aliphatic aldehydes.
Place, publisher, year, edition, pages
Stockholm: KTH , 2009. , 54 p.
Trita-CHE-Report, ISSN 1654-1081 ; 2009:12
acyl cyanides, asymmetric synthesis, biocatalysis, cyanide, cyanohydrins, dual activation, enzymes, high-throughput screening, Lewis acid, Lewis base, metal catalysis, minor enantiomer recycling, salen, titanium
IdentifiersURN: urn:nbn:se:kth:diva-10205ISBN: 978-91-7415-263-0OAI: oai:DiVA.org:kth-10205DiVA: diva2:210859
2009-05-08, F3, Lindstedtsvägen 26, Stockholm, 10:00 (English)
List, Benjamin, Prof.
Moberg, Christina, professor
QC 201008182009-05-072009-04-062010-09-22Bibliographically approved
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