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Highly Flexible Synthesis of Chiral Azacycles via Iridium-Catalyzed Hydrogenation
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
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2010 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 132, no 26, 8880-8881 p.Article in journal (Refereed) Published
Abstract [en]

A range of saturated chiral azacycles has been prepared in high yield and with high selectivity from simple starting materials. A modular approach with ring-closing metathesis as a key step was used to produce a number of five-, six-, and seven-membered cyclic alkenes. Asymmetric hydrogenation catalyzed by N,P-ligated iridium complexes gave saturated azacycles in high optical purity. This methodology was demonstrated in the synthesis of a pharmaceutical precursor.

Place, publisher, year, edition, pages
2010. Vol. 132, no 26, 8880-8881 p.
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-135809DOI: 10.1021/ja103901eISI: 000279561200033PubMedID: 20557052OAI: oai:DiVA.org:uu-135809DiVA: diva2:375902
Available from: 2010-12-09 Created: 2010-12-08 Last updated: 2017-12-11Bibliographically approved
In thesis
1. Studies of Hydrogenations and Isomerizations of Olefins and Alkylations of Amines Using Iridium Catalysts
Open this publication in new window or tab >>Studies of Hydrogenations and Isomerizations of Olefins and Alkylations of Amines Using Iridium Catalysts
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis describes three types of reactions that were carried out using iridium catalysts.

The first type is the iridium-catalyzed asymmetric hydrogenation of olefins. In paper I, the preparation of a new type of bicyclic thiazole-phosphine based iridium complex was described. The new catalysts have displayed high activity and enantioselectivity in the asymmetric hydrogenation of unfunctionalized olefins. Papers II and III focus on the expansion of the substrate scope for the iridium catalyzed asymmetric hydrogenation in which a number of heterocyclic olefins were evaluated. In paper IV, the enantioselective asymmetric hydrogenation of α, β-unsaturated esters was described. The chiral products bearing tertiary stereogenic centers obtained by hydrogenation have great synthetic value and have been used in the synthesis of pharmaceuticals as well as in the total synthesis of natural products.

The second type is the asymmetric isomerization of allylic alcohols. In paper V, both cis and trans primary allylic alcohols were isomerized to the corresponding β-chiral aldehydes in high enantioselectivities by an N,P-chelating iridium complex.

The third type is the selective mono-N-alkylation of amines with alcohols. In paper VI, a phosphine/NHC based iridium catalyst was synthesized and applied in the alkylation of amines. It is the first time that this type of transformation is carried out at room temperature.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 65 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 982
Keyword
Iridium, Asymmetric, Hydrogenation, Isomerization, Alkylation
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-182647 (URN)978-91-554-8502-3 (ISBN)
Public defence
2012-11-28, B21, BMC, Husaragatan 3, Uppsala, 10:15 (English)
Opponent
Supervisors
Available from: 2012-11-07 Created: 2012-10-14 Last updated: 2013-01-23
2. Transition Metal Catalysis for Selective Synthesis and Sustainable Chemistry
Open this publication in new window or tab >>Transition Metal Catalysis for Selective Synthesis and Sustainable Chemistry
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis discusses the preparation and use of transition-metal catalysts for selective organic chemical reactions. Specifically, two different matters have been studied; the asymmetric hydrogenation of carbon-carbon double bonds using N,P-ligated iridium catalysts and the metal-catalyzed transfer of small molecules from biomass to synthetic intermediates.

In the first part of this thesis, chiral N,P-ligands were synthesized and evaluated in iridium catalysts for the asymmetric hydrogenation of non- and weakly functionalized alkenes (Papers I & II). The new catalysts were prepared via chiral-pool strategies and exhibited superior properties for the reduction of certain types of alkenes. In particular, some of the catalysts showed excellent activity and selectivity in the enantioselective reduction of terminal alkenes, and the preparation of a modular catalyst library allowed the asymmetric hydrogenation of a wide range of 1,1-disubstituted alkenes with unprecedented efficiency and enantioselectivity (Paper III). Methods for the selective preparation of chiral hetero- and carbocyclic fragments using iridium-catalyzed asymmetric hydrogenation as an enantiodetermining key step were also developed. A range of elusive chiral building blocks that have applications in pharmaceutical and natural-product chemistry could thus be conveniently prepared (Papers IV & V).

The second part of this thesis deals with the catalytic decomposition of polysaccharides into sugar alcohols and the incorporation of their decomposition products into alkene substrates. Iridium-catalyzed dehydrogenative decarbonylation was found to decompose polyols into CO:H2 mixtures that could be used immediately in the ex situ low-pressure hydroformylation of styrene (Paper VI). The net process was thus the hydroformylation of alkenes with biomass-derived synthesis gas.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 125 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 984
Keyword
Catalysis, Transition metals, Asymmetric catalysis, Hydrogenation, Sustainable chemistry
National Category
Organic Chemistry
Research subject
Chemistry with specialization in Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-182900 (URN)978-91-554-8507-8 (ISBN)
Public defence
2012-11-30, B42, BMC, Husargatan 3, Uppsala, 10:00 (English)
Opponent
Supervisors
Available from: 2012-11-09 Created: 2012-10-18 Last updated: 2013-01-23
3. Asymmetric Hydrogenation of Functionalized Olefins Using N,P-Ligated Iridium Complexes
Open this publication in new window or tab >>Asymmetric Hydrogenation of Functionalized Olefins Using N,P-Ligated Iridium Complexes
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Transition-metal-catalyzed asymmetric hydrogenation is one of the most efficient, straightforward, and well-established methods for preparing enantiomerically enriched compounds. Over the past decades, significant progress has been made with iridium, rhodium and ruthenium complexes to asymmetric hydrogenate a selection of olefins, such as, α,β-unsaturated carboxylic acid derivatives, ketones, imines and phosphonates. Although these metals have been applied successfully in the hydrogenation of olefins, they differ in their substrate tolerance.  Ruthenium and rhodium based catalysts require a coordinating group in the vicinity of the C=C bond. However, iridium based catalysts do not require this coordinating group, hence, asymmetric hydrogenation with iridium catalysts has been widely used for both functionalized and unfunctionalized olefin substrates. This thesis focuses on expanding the substrate scope for asymmetric hydrogenation using chiral N,P-ligated iridium catalysts. Papers I and II investigate the asymmetric hydrogenation of prochiral N-heterocyclic compounds prepared by ring-closing metathesis using the iridium catalysts developed in our group.  These substrates are interesting as they bear resemblance to pharmaceutically active compounds and therefore have tremendous value in medicinal chemistry.  Excellent enantioselectivities, up to >99% ee and conversions were obtained. In papers III and IV we synthesized many unsaturated acyclic and cyclic sulfones with varying substitution patterns.  The sulfones were subjected to hydrogenation using our N,P-ligated iridium catalysts, producing the chiral sulfone products in high enantiomeric excess (up to 99% ee). This methodology was combined with the Ramberg-Bäcklund reaction, offering a novel route to chiral allylic and homoallylic compounds. In addition to obtaining these chiral compounds in good yields, no decrease in enantiomeric excess was observed after the Ramberg-Bäcklund reaction. This strategy has been applied in the preparation of the chiral building block for renin inhibitors.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 59 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 983
Keyword
asymmetric hydrogenation, iridium, Ramberg-Bäcklund reaction, sulfone, heterocycle, preclamol, remikiren
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-182648 (URN)978-91-554-8503-0 (ISBN)
Public defence
2012-11-29, A1:107A, BMC, Husargatan 3, Uppsala, 10:15 (English)
Opponent
Supervisors
Available from: 2012-11-07 Created: 2012-10-14 Last updated: 2013-01-23

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