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A Mechanistic Investigation of the Kinetic Resolution of Secondary Aromatic Alcohols Using a Ferrocene-Based Planar Chiral 4-(Dimethylamino)pyridine Catalyst
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Synthetical Organic Chemistry.
KTH Royal Institute of Technology.
2015 (English)In: CHEMISTRY-A EUROPEAN JOURNAL, ISSN 0947-6539, Vol. 21, no 14, 5623-5631 p.Article in journal (Refereed) Published
Abstract [en]

A detailed kinetic analysis for the acetylation of 1-phenylethanol with acetic anhydride catalyzed by the planar chiral DMAP catalyst (–)-1 is presented. The study include a computational investigation of the potential energy surface including the rate-limiting and stereoselective transitionstates at the DFT level of theory. The kinetic study suggests that the reaction proceeds with first order in catalyst and in 1-phenylethanol, while the acetic anhydride shows a fractional order. The fractional order is racionalized based on an equilibrium between the free and the acetylated catalyst.

Place, publisher, year, edition, pages
2015. Vol. 21, no 14, 5623-5631 p.
Keyword [en]
Reaction progress kinetic analysis, DFT calculation
National Category
Organic Chemistry
URN: urn:nbn:se:uu:diva-233714DOI: 10.1002/chem.201405793ISI: 000352504500041PubMedID: 25677932OAI: oai:DiVA.org:uu-233714DiVA: diva2:753955
Available from: 2014-10-09 Created: 2014-10-08 Last updated: 2015-05-12Bibliographically approved
In thesis
1. Organocatalytic Acylation for the Kinetic Resolution of Secondary Aryl Alcohols: Synthetic Applications and Mechanistic Studies
Open this publication in new window or tab >>Organocatalytic Acylation for the Kinetic Resolution of Secondary Aryl Alcohols: Synthetic Applications and Mechanistic Studies
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The research described in this thesis focuses on the catalytic acylative kinetic resolution (KR) of aromatic secondary alcohols, using a planar-chiral 4-(dimethylamino)pyridine (DMAP) organocatalyst.

In the first part of this thesis, the substrate scope of the above mentioned process was expanded to aromatic secondary alcohols that contain an extra functional group in the alkyl moiety, such as 1,2-azido alcohols, 2-hydroxy-2-aryl-ethylphosphonates and 2-hydroxy-2-aryl esters. Thus, the preparation of highly functionalized compounds in their enantiomerically pure form with excellent enantiomeric excess (up to 99% ee) was achieved. Furthermore, the synthetic applicability of this methodology was illustrated through the synthesis of two high value compounds, (R)-Pronethalol and (S)-3-hydroxy-N-methyl-3-phenylpropanamide, which is an immediate precursor of bioactive molecules such as (S)-Fluoxetine.

The second part of this thesis deals with the mechanistic study of the acylative KR catalyzed by the planar-chiral DMAP derivative. Reaction Progress Kinetic Analysis methodology was used in the investigation of the reaction mechanism, probing that no notable product inhibition or decomposition of the catalyst occurs in the studied system. The reaction rate showed fractional order dependence on the concentration of both reactants. Furthermore, NMR spectroscopy was utilized to study the equilibrium between the different catalyst states, which explains the measured kinetics of the reaction.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. 54 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1191
kinetic resolution, organocatalysis, secondary alcohols, reaction progress kinetic analysis
National Category
Organic Chemistry
Research subject
Chemistry with specialization in Organic Chemistry
urn:nbn:se:uu:diva-233734 (URN)978-91-554-9075-1 (ISBN)
Public defence
2014-11-28, A1:111a, BMC, Husargatan 3, Uppsala, 09:00 (English)
Available from: 2014-11-07 Created: 2014-10-09 Last updated: 2015-02-03

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