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Synthesis and Evaluation of N,P-Chelating Ligands in Asymmetric Transition-Metal-Catalyzed Reactions: Ir-Catalyzed Asymmetric Hydrogenation and Pd-Catalyzed Asymmetric Intermolecular Heck Reaction
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry. (PGA)
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis describes synthesis of new chiral N,P ligands and their evaluation in two types of asymmetric transition-metal catalyzed reactions.

The first part of the thesis describes studies in iridium-catalyzed asymmetric hydrogenation. A new class of chiral N,P ligands, imidazole-phosphines, was synthesized and evaluated in the Ir-catalyzed asymmetric hydrogenation of olefins (Paper I). The new ligands proved to be highly efficient and enantioselective in the reaction. Because the substrate scope of Ir-catalyzed asymmetric hydrogenation is still limited to certain types of test substrates, new substrate classes with importance in medicinal and materials chemistry were investigated. Vinyl fluorides were efficiently hydrogenated to fluorine-containing chiral centers by the iridium catalysts with imidazole-phosphine ligands (Paper I). To obtain CF3-bearing chiral centers, we hydrogenated CF3-substituted olefins (Paper II). Ir-catalyzed asymmetric  hydrogenation was highly enantioselective for the functionalized CF3-substituted olefins and the resulting chiral products can be valuable in design of materials such as LCD screens. Ir-catalyzed asymmetric hydrogenation was also evaluated as a route to diarylmethine chiral centers (Paper III). A wide range of new chiral compounds possessing a diarylmethine chiral center was obtained.

The second part of the thesis deals with asymmetric intermolecular Heck reaction utilizing N,P ligands. The N,P ligand class of thiazole-phosphines was evaluated in the Heck reaction (Paper IV) and gave high enantioselectivity. Further, the intermolecular Heck reaction was examined using computational and experimental studies (Paper V). This study led to a better understanding of the enantioselectivity in the reaction.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2009. , p. 74
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 681
Keywords [en]
Asymmetric hydrogenation, Heck reaction, N, P ligand, Iridium, Palladium, Asymmetric catalysis, Alkenes, Fluorine, Diarylmethine stereocenters
National Category
Chemical Sciences
Research subject
Organic Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-108940ISBN: 978-91-554-7632-8 (print)OAI: oai:DiVA.org:uu-108940DiVA, id: diva2:272780
Public defence
2009-11-26, sal B41, BMC, Husargatan 3, Uppsala, 10:15 (English)
Opponent
Supervisors
Available from: 2009-11-05 Created: 2009-10-05 Last updated: 2009-11-05Bibliographically approved
List of papers
1. Highly Selective Iridium-Catalyzed Asymmetric Hydrogenation of Trifluoromethyl Olefins: A New Route to Trifluoromethyl-Bearing Stereocenters
Open this publication in new window or tab >>Highly Selective Iridium-Catalyzed Asymmetric Hydrogenation of Trifluoromethyl Olefins: A New Route to Trifluoromethyl-Bearing Stereocenters
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2009 (English)In: Advanced Synthesis and Catalysis, ISSN 1615-4150, E-ISSN 1615-4169, Vol. 351, no 3, p. 375-378Article in journal (Refereed) Published
Abstract [en]

Fluorine-containing compounds are useful in many applications ranging from pharmaceuticals to ferroelectric crystals. We have developed a new, highly enantioselective synthetic route to trifluoromethyl-bearing stereocenters in up to 96% ee via asymmetric hydrogenation using N,P-ligated iridium catalysts. We also hydrogenated an isomeric mixture of olefins; this reaction gave the hydrogenation product highly enantioselectively (87% ee), and only the E isomer was present after the reaction had reached 56% conversion.

Keywords
asymmetric catalysis, fluorine, hydrogenation, iridium, P-N ligands
National Category
Analytical Chemistry
Research subject
Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-100634 (URN)10.1002/adsc.200800645 (DOI)000264058900016 ()
Available from: 2009-04-03 Created: 2009-04-03 Last updated: 2017-12-13Bibliographically approved
2. Combined Experimental and Theoretical Study of the Mechanism and Enantioselectivity of Palladium-Catalyzed Intermolecular Heck Coupling
Open this publication in new window or tab >>Combined Experimental and Theoretical Study of the Mechanism and Enantioselectivity of Palladium-Catalyzed Intermolecular Heck Coupling
2008 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 130, no 31, p. 10414-10421Article in journal (Refereed) Published
Abstract [en]

The asymmetric Heck reaction using P,N-ligands has been studied by a combination of theoretical and experimental methods. The reaction follows Halpern-style selectivity, that is, the major isomer is produced from the least favored form of the pre-insertion intermediate. The initially formed Ph-Pd(P,N) species prefers a geometry with the phenyl trans to N. However, the alternative form, with Ph trans to P, is much less stable but much more reactive. In the preferred transition state, the phenyl moiety is trans to P, but significant electron density has been transferred to the alkene carbon trans to N. The steric interactions in this transition state fully account for the enantioselectivity observed with the ligands studied. The calculations also predict relative reactivity and nonlinear mixing effects for the investigated ligands, these predictions are fully validated by experimental testing. Finally, the low conversion observed with some catalysts was found to be caused by inactivation due to weak binding of the ligand to Pd(0). Adding monodentate PPh3 alleviated the precipitation problem without deteriorating the enantioselectivity and led to one of the most effective catalytic systems to date.

National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-17847 (URN)10.1021/ja802991y (DOI)000258080600064 ()
Available from: 2008-09-05 Created: 2008-09-05 Last updated: 2017-12-08Bibliographically approved
3. Iridium Catalysts with Chiral Imidazole-Phosphine Ligands for Asymmetric Hydrogenation of Vinyl Fluorides and other Olefins
Open this publication in new window or tab >>Iridium Catalysts with Chiral Imidazole-Phosphine Ligands for Asymmetric Hydrogenation of Vinyl Fluorides and other Olefins
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2008 (English)In: Advanced Synthesis and Catalysis, ISSN 1615-4150, E-ISSN 1615-4169, Vol. 350, no 7-8, p. 1168-1176Article in journal (Refereed) Published
Abstract [en]

New chiral bidentate imidazole-phosphine ligands have been prepared and evaluated for the iridium-catalysed asymmetric hydrogenation of olefins. The imidazole-phosphine-ligated iridium catalysts hydrogenated trisubstituted olefins with the same sense of enantiodiscrimination as known iridium catalysts possessing oxazole and thiazole as N-donors. The imidazole-based catalysts were shown to hydrogenate vinyl fluorides, in some cases with the highest ee values published to date.

Keywords
asymmetric hydrogenation, iridium, N, P donating ligand, vinyl fluorides
National Category
Analytical Chemistry Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-99805 (URN)10.1002/adsc.200800062 (DOI)
Available from: 2009-03-20 Created: 2009-03-20 Last updated: 2017-12-13Bibliographically approved
4. Microwave-Assisted Asymmetric Intermolecular Heck Reaction using Phosphine-Thiazole Ligands
Open this publication in new window or tab >>Microwave-Assisted Asymmetric Intermolecular Heck Reaction using Phosphine-Thiazole Ligands
2007 (English)In: Advanced Synthesis and Catalysis, ISSN 1615-4150, E-ISSN 1615-4169, Vol. 349, no 7-18, p. 2595-2602Article in journal (Refereed) Published
Abstract [en]

A series of new phosphine-thiazole compounds has been synthesized and used as efficient ligands in the palladium-catalyzed asymmetric intermolecular Heck coupling of 2,3-dihydrofuran with aryl triflates and cyclohexenyl triflate. Microwave heating was used to accelerate the reactions and gave complete conversions in as little as one hour. Products were obtained with good to excellent enantioselectivities.

Keywords
asymmetric catalysis, Heck reaction, microwave heating, phosphine-thiazole ligands
National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-12345 (URN)10.1002/adsc.200700390 (DOI)
Available from: 2007-12-13 Created: 2007-12-13 Last updated: 2017-12-11Bibliographically approved
5. Iridium-Catalyzed Asymmetric Hydrogenation yielding Chiral Diarylmethines with Weakly Coordinating or Noncoordinating Substituents
Open this publication in new window or tab >>Iridium-Catalyzed Asymmetric Hydrogenation yielding Chiral Diarylmethines with Weakly Coordinating or Noncoordinating Substituents
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2009 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 131, no 25, p. 8855-8860Article in journal (Refereed) Published
Abstract [en]

Diarylimethine-containing stereocenters are present in pharmaceuticals   and natural products, making the synthetic methods that form these   chiral centers are important in industry. We have applied iridium   complexes with novel N,P-chelating ligands to the asymmetric  hydrogenation of trisubstituted olefins, forming diarylmethine chiral   centers in high conversions and excellent enantioselectivities (up to   99% ee) for a broad range of substrates. Our results support the hypothesis that steric hindrance in one specific area of the catalyst   is playing a key role in stereoselection, as the hydrogenation of   substrates differing little at the prochiral carbon occurred with high enantioselectivity. As a result, excellent stereodiscrimination was obtained even when the prochiral carbon bore, for example, phenyl and p-tolyl groups.

National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-99807 (URN)10.1021/ja9013375 (DOI)000267631000039 ()19552449 (PubMedID)
Available from: 2009-03-20 Created: 2009-03-20 Last updated: 2017-12-13Bibliographically approved

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