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Fast Synthesis of Aryl Triflates with Controlled Microwave Heating
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
2002 (English)In: Organic Letters, ISSN 1523-7060, Vol. 4, no 7, 1231-1233 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2002. Vol. 4, no 7, 1231-1233 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-93597OAI: oai:DiVA.org:uu-93597DiVA: diva2:167124
Available from: 2005-10-20 Created: 2005-10-20 Last updated: 2013-07-04Bibliographically approved
In thesis
1. New Methods for the Synthesis of 3-Substituted 1-Indanones: A Palladium-Catalyzed Approach
Open this publication in new window or tab >>New Methods for the Synthesis of 3-Substituted 1-Indanones: A Palladium-Catalyzed Approach
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In medicinal chemistry, there is a constant need for new preparative methods, both to make the synthesis process more effective, and to increase the accessibility to a wide variety of compounds. A number of different approaches can be used to attain these goals. Transition metal catalysis is generally performed under mild conditions, providing both regio- and chemoselective reactions. Thus, it offers an attractive means of preparation of complex drug candidates. Two additional methodologies used to increase the preparative efficiency are one-pot protocols and controlled microwave heating. One-pot and multi-component reactions are less time consuming than step-by-step reactions, and microwave heating has been used to considerably shorten the reaction times.

This thesis describes a new palladium-catalyzed, one-pot reaction producing racemic acetal-protected 3-hydroxy-1-indanones from ethylene glycol vinyl ether and triflates of salicylic aldehydes. The triflates were prepared using controlled microwave heating. The reaction sequence starts with a regioselective internal Heck coupling, followed by an annulation cascade. By including secondary amines in the reaction mixture, the reaction was further developed into a three-component reaction delivering racemic acetal-protected 3-amino-1-indanones. This new method was utilized for the synthesis of primary, secondary and tertiary aminoindanones. Finally, by using enantiopure t-butyl sulfinyl imines, derived from salicylic aldehyde triflates and ethylene glycol vinyl ether as starting materials in a closely related type of palladium coupling–annulation sequence, a stereoselective protocol providing enantiomerically pure 3-amino-1-indanones was developed. To demonstrate an application in medicinal chemistry, the enantiopure 3-amino-1-indanones were incorporated as P2 and/or P2´ substituents into active HIV-1 protease inhibitors.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 66 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 18
Keyword
Organic chemistry, Heck, palladium, indanone, annulation, microwave heating, triflate, sulfinyl imine, HIV-1 protease inhibitor, Organisk kemi
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-6015 (URN)91-554-6366-5 (ISBN)
Public defence
2005-11-11, B22, BMC, Husargatan 5, Uppsala, 09:15
Opponent
Supervisors
Available from: 2005-10-20 Created: 2005-10-20Bibliographically approved

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Larhed, Mats

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