Ruthenium-Catalyzed Hydrogen Transfer Reactions: Mechanistic Studies and Chemoenzymatic Dynamic Kinetic Resolutions
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
The main focus of this thesis lies on transition metal-catalyzed hydrogen transfer reactions. In the first part of the thesis, the mechanism for racemization of sec-alcohols with a ruthenium complex, Ru(CO)2Cl(η5-C5Ph5) was studied.
The reaction between 5-hexen-2-ol and Ru(CO)2(Ot-Bu)(η5-C5Ph5) was studied with the aim to elucidate the origin of the slow racemization observed for this sec-alcohol. Two diastereomers of an alkoxycarbonyl complex, which has the double bond coordinated to ruthenium, were characterized by NMR and in situ FT-IR spectroscopy. The observed inhibition of the rate of racemization for substrates with double bonds provided further confirmation of the importance of a free coordination site on ruthenium for β-hydride elimination. Furthermore, we observed that CO exchange, monitored by 13C NMR using 13CO, occurs with both the precatalyst, Ru(CO)2Cl(η5-C5Ph5), and the active catalytic intermediate, Ru(CO)2(Ot-Bu)(η5-C5Ph5). It was also found that added CO has an inhibitory effect on the rate of racemization of (S)-1-phenylethanol. Both these observations provide strong support for reversible CO dissociation as a key step in the racemization mechanism.
In the second part of this thesis, Ru(CO)2Cl(η5-C5Ph5) was combined with an enzymatic resolution catalyzed by a lipase, leading to several efficient dynamic kinetic resolutions (DKR). DKR of exocyclic allylic alcohols afforded the corresponding acetates in high yields and with excellent enantiomeric excess (ee). The products were utilized as synthetic precursors for α-substituted ketones and lactones. DKR of a wide range of homoallylic alcohols afforded the products in good to high yields and with high ee. The homoallylic acetates were transformed into 5,6-dihydropyran-2-ones in a short reaction sequence. Furthermore, DKR of a wide range of aromatic β-chloroalcohols afforded the products in high yields and with excellent ee. The β-chloro acetates were further transformed into chiral epoxides.
Place, publisher, year, edition, pages
Stockholm: Department of Organic Chemistry, Stockholm University , 2013. , 84 p.
Hydrogen transfer, ruthenium catalysis, kinetic resolution, dynamic kinetic resolution, racemization, asymmetric synthesis
Research subject Organic Chemistry
IdentifiersURN: urn:nbn:se:su:diva-89263ISBN: 978-91-7447-706-1OAI: oai:DiVA.org:su-89263DiVA: diva2:616629
2013-05-24, Magnélisalen, Kemiska Övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Pfaltz, Andreas, Professor
Bäckvall, Jan-Erling, Professor
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 5: Mansucript.2013-04-182013-04-172013-11-06Bibliographically approved
List of papers