Phosphoramidite ligands and artificial metalloenzymes in enantioselective rhodium-catalysis Panella, Lavinia

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1 University of Groningen Phosphoramidite ligands and artificial metalloenzymes in enantioselective rhodium-catalysis Panella, Lavinia IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2006 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Panella, L. (2006). Phosphoramidite ligands and artificial metalloenzymes in enantioselective rhodiumcatalysis: old challenges and new frontiers s.n. Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date:

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3 The work described in this thesis was carried out at the department of Organic and Molecular Inorganic Chemistry, Stratingh Institute, University of Groningen, the Netherlands. The work described in this thesis was financially supported by the Dutch Organization for Scientific Research (NWO-STW): project Printed by: Wöhrmann Print Service, Zutphen, the Netherlands. ISBN: ISBN: (electronic version)

4 RIJKSUNIVERSITEIT GRONINGEN Phosphoramidite Ligands and Artificial Metalloenzymes in Enantioselective Rhodium-Catalysis: Old Challenges and New Frontiers Proefschrift ter verkrijging van het doctoraat in de Wiskunde en Natuurwetenschappen aan de Rijksuniversiteit Groningen op gezag van de Rector Magnificus, dr. F. Zwarts, in het openbaar te verdedigen op vrijdag 15 september 2006 om uur door Lavinia Panella geboren op 13 april 1972 te Monselice (Italië)

5 Promotores: Prof. Dr. J.G. de Vries Prof. Dr. Ir. A.J. Minnaard Prof. Dr. B.L. Feringa Beoordelingscommissie: Prof. Dr. J.B.F.N. Engberts Prof. Dr. D.B. Janssen Prof. Dr. P.C.J. Kamer ISBN:

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8 Contents Chapter 1 Introduction 1.1 Catalysis: classification and characteristics Homogeneous catalysis using transition metal complexes Chiral intermediates Rh-catalyzed asymmetric hydrogenation Monodentate chiral phosphoramidite ligands Enantiopure α-amino acids Chiral secondary alcohols Rh-catalyzed asymmetric hydroformylation Aim of this thesis References and notes 30 Chapter 2 Enantioselective Rh-Catalyzed Hydrogenation of Enol Carbamates with Monodentate Phosphoramidites 2.1 Introduction Hydrogenation of enol acetates Earlier work and aim of this study Synthesis of 1-aryl-vinyl acetates Asymmetric hydrogenation of 1-aryl-vinyl acetates Synthesis of 1-phenyl-vinyl N,N-dialkyl carbamates Vinyl carbamates as bidentate substrates Hydrogenation of 1-phenyl-vinyl N,N-dialkyl carbamates Expanding the scope of the use of vinyl carbamates Hydrogenation of a range of a-substituted vinyl N,N-diethyl 62 carbamates 2.11 Conclusions and outlook Experimental section References and notes 80 Chapter 3 Enantioselective Rh-Catalyzed Hydrogenation of N-Formyl Dehydroamino Esters with Monodentate Phosphoramidite Ligands 3.1 Introduction Dehydroamino esters synthesis Amine protecting groups Scope of this study 90

9 3.5 Precedents of the N-formyl as stereo-directing group Synthesis of N-formyl dehydroamino esters Some insight into the reaction mechanism using Lewis acids Isomers and rotamers Preparation and use of methyl 2-(formamido)acrylate (3.63) Asymmetric hydrogenation of N-formyl dehydroamino esters β,β-disubstituted α-dehydroamino esters Hydrogenation of 2-formamidoacrylic acid (3.77) N-formyl: from directing to protecting group Conclusions Outlook Experimental section References and notes 134 Chapter 4 Rh-Catalyzed Asymmetric Hydroformylation Using Phosphoramidite Ligands: a Preliminary Study 4.1 Introduction Monodentate phosphorus-based ligands in Rh-catalyzed asymmetric 144 hydroformylation 4.3 Rh-catalyzed hydroformylation of styrene (4.1a) Rh-catalyzed hydroformylation of vinyl acetate (4.1b) Bidentate phosphoramidite ligands in the Rh-catalyzed 152 hydroformylation of styrene (4.1a) and vinyl acetate (4.1b) 4.6 Conclusions and outlook Further developments Experimental section References and notes 162 Chapter 5 Merging Homogeneous Catalysis with Biocatalysis: Papain as Hydrogenation Catalysts 5.1 Introduction Scope of this study The pioneering work of Kaiser and Whitesides Artificial metalloproteins: state of the art The importance of the appropriate strategy Cysteine proteases: papain Low molecular weight synthetic inhibitors Cofactor design 193

10 5.9 Cofactor synthesis Cofactor solubility tests Papain pretreatment and activity test Alkylation of papain using linker 5.58b and cofactor 5.47a Improvements in the cofactor design Alkylation of papain using linker 5.72 and cofactor 5.47c ESI-MS analysis of the modified papain adduct PapPhos Digestion of PapPhos (5.77) and tandem mass spectrometry of 219 peptide Asn 18 -Lys 39 containing Cys Kinetic parameters for the alkylation process Scaling up the preparation of PapPhos (5.77) Rh-catalyzed hydroformylation in aqueous media Rh-catalyzed hydrogenation in aqueous media Complexation of PapPhos (5.77) with Rh(COD) 2 BF Hydrogenation of methyl 2-(acetamido)acrylate (5.81) after the new 241 purification procedure of complex Conclusions and outlook Experimental section References and notes 253 Samenvatting 263