UvA-DARE (Digital Academic Repository) Fluorogenic organocatalytic reactions Raeisolsadati Oskouei, M. Link to publication Citation for published version (APA): Raeisolsadati Oskouei, M. (2017). Fluorogenic organocatalytic reactions. General rights 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), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (http://dare.uva.nl) Download date: 08 Apr 2019
Invitation To the public defence of my thesis entitiled: Fluorogenic Organocatalytic Reactions Fluorogenic Organocatalytic Reactions Fluorogenic Organocatalytic Reactions On Tuesday 25th of April at 10:00 a.m. Agnietenkapel, Oudezijds Voorburgwal 231, 1012 EZ Amsterdam Mina Raeisolsadati Oskouei mraeisolsadati@gmail.com Mina Raeisolsadati Oskouei Paranymphs: Mina Raeisolsadati Oskouei Dongdong Zheng D.Zheng@uva.nl Jing Zuo J.Zuo@uva.nl Fluorogenic Organocatalytic Reactions Processed on: 7-3-2017 508735-L-bw-Oskouei
Fluorogenic Organocatalytic Reactions Mina Raeisolsadati Oskouei Fluorogenic Organocatalytic Reactions Fluorogenic Organocatalytic Reactions Mina Raeisolsadati Oskouei 508735-L-bw-Oskouei Processed on: 7-3-2017 Invitation Jing Zuo J.Zuo@uva.nl Dongdong Zheng D.Zheng@uva.nl Paranymphs: mraeisolsadati@gmail.com Mina Raeisolsadati Oskouei Agnietenkapel, Oudezijds Voorburgwal 231, 1012 EZ Amsterdam On Tuesday 25th of April at 10:00 a.m. Fluorogenic Organocatalytic Reactions To the public defence of my thesis entitiled:
Fluorogenic Organocatalytic Reactions ACADEMISCH PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Universiteit van Amsterdam op gezag van de Rector Magnificus prof. dr. ir. K.I.J. Maex ten overstaan van een door het College voor Promoties ingestelde commissie, in het openbaar te verdedigen in de Agnietenkapel op dinsdag 25 april 2017 te 10:00 uur door Mina Raeisolsadati Oskouei geboren te Tabriz, Iran
Promotiecommissie: Promotor: Prof. dr. A. M. Brouwer Universiteit van Amsterdam Copromotor: Prof. dr. H. Hiemstra Universiteit van Amsterdam Overige leden: Prof. dr. W. J. Buma Universiteit van Amsterdam Dr. M. A. Fernández-Ibáñez Universiteit van Amsterdam Prof. dr. J. H. van Maarseveen Universiteit van Amsterdam Prof. dr. F. P. J. T. Rutjes Radboud Universiteit Prof. dr. S. Woutersen Universiteit van Amsterdam Faculteit der Natuurwetenschappen, Wiskunde en Informatica The research covered in this thesis was conducted in the Molecular Photonics group at the Van t Hoff Institute for Molecular Sciences, University of Amsterdam.
To Karim and Juliette
Contents Abbreviations Chapter 1. Introduction 1 1.1. Organocatalysis.. 1 1.1.1. Cinchona alkaloid based organocatalysts.... 3 1.1.2. Thiourea based organocatalysts.. 6 1.2. Fluorescence spectroscopy... 7 1.3. Fluorogenic reactions. 10 1.4. BODIPYs as the suitable candidates for fluorogenic reactions... 12 1.5. Outline of the research 13 References.. 15 Chapter 2. Experimental methods and characterization. 23 2.1. General information..... 23 2.2. Synthesis of the substrate BODIPYs.. 26 2.2.1. Synthesis of compound 6.... 27 2.2.2. Synthesis of compound 7. 28 2.2.3. Synthesis of compound 8. 28 2.2.4. Synthesis of compound 9. 29 2.2.5. Synthesis of compound 10. 29 2.2.6. Synthesis of compound 15.. 29 2.2.6.1. Synthesis of compound 12. 30 2.2.7. Synthesis of compound 17. 31 2.3. Synthesis of the catalysts. 31 2.3.1. Synthesis of dimethyl amino cyclohexyl amine... 31 2.3.2. Synthesis of catalyst 25... 32 2.3.3. Synthesis of catalyst 26... 32 2.3.4. Synthesis of catalysts 27. 32 2.3.5. Synthesis of catalyst 28... 33 2.3.6. Synthesis of catalyst 29... 33 2.3.7. General procedure for Immobilization of the catalysts on the surface of glass cover slips... 34 2.3.7.1. Cover slips cleaning..... 34 2.3.7.2. Cover slips modification. 34 2.3.7.3. Catalysts immobilization.. 34 2.3.8. Synthesis of catalyst 32 35 2.4. Synthesis of the product BODIPYs... 35 2.4.1. General procedure for the synthesis of compound 38 35 2.4.2. General procedure for the synthesis of compound 39 36 2.4.3. General procedure for the synthesis of compound 40 36 2.4.4. General procedure for the synthesis of compound 41 37 2.4.5. General procedure for the synthesis of compound 42 38 i
2.4.6. General procedure for the synthesis of compound 43 38 2.4.7. General procedure for the synthesis of compound 44.. 39 References 40 Chapter 3. Fluorescence turn-on in organocatalytic Michael reactions 43 3.1. Introduction. 43 3.2. Michael reaction of compound 15 with benzyl mercaptan in the presence of different organocatalysts.. 44 3.3. Following the Michael reaction of compound 15 with benzyl mercaptan in the presence of hydrogen bond donating organocatalysts using fluorescence spectroscopy.. 48 3.4. Following the Michael reaction of compound 15 with benzyl mercaptan in the presence of immobilized organocatalysts using fluorescence spectroscopy 54 3.5. Following the Michael reaction of compound 15 with benzyl mercaptan in the presence of a fluorescent organocatalyst.... 57 3.6. Michael addition reaction between compound 17 and benzyl mercaptan. 59 3.7. Michael addition of reaction compound 15 and dimethylmalonate. 63 3.8. Reaction of the BODIPY-Maleimide and BODIPY-Nitroalkene with carbon nucleophiles... 64 3.9. Conclusion.. 66 References. 66 Chapter 4. Organocatalytic synthesis of fluorescent chromenes... 73 4.1. Chromenes and fluorogenic reactions... 73 4.2. Fluorescent Chromenes... 76 References.... 83 Chapter 5. Organocatalytic Biginelli reaction.. 87 5.1. Introduction.. 87 5.2. Fluorescent derivative of DHPM.. 88 5.3. Discussion... 94 5.4. Conclusion.. 98 References. 98 Chapter 6. Towards Single Molecule Detection of Organocatalytic Reactions 105 6.1. Introduction.. 105 6.2. Imaging with TIRFM. 107 6.3. Experiment Design. 109 6.4. TIRFM of organocatalytic Michael addition of benzyl mercaptan to compound 15.. 111 6.4. Conclusion.. 118 References. 119 ii
Publication from this Thesis.... 123 Summary.... 125 Samenvatting.. 129 Acknowledgments 133 iii
Abbreviations AIBN BINOL BnCl Boc-L-Proline BODIPY BzCl CFM DCE DCM DDQ DHPMs DIEA DMF DMSO EDCI ee emccd EtOAc FRET HOAc HOBt HPLC mcpba NOBIN NSOM PET PMT scmos SEM TADDOLS TCSPC TFA TFAA THF TIRFM TLC Azobisisobutyronitrile 1,1 -Bi-2-naphthol Benzyl chloride N-(tert-Butoxycarbonyl)-L-proline Boron-dipyrromethene Benzoyl chloride Confocal microscopy Dichloroethane Dichloromethane 2,3-Dichloro-5,6-dicyanobenzoquinone Dihydropyrimidinones N,N-Diisopropylethylamine Dimethylformamide Dimethyl sulfoxide 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Enantiomeric excess Electron multiplying charge coupled device Ethyl acetate Förster resonance energy transfer Acetic acid Hydroxybenzotriazole High performance liquid chromatography 3-Chloroperbenzoic acid 2-Amino-2'-hydroxy-1,1'-binaphthyl Near-field scanning optical microscopy Photoinduced electron transfer Photomultiplier Scientific complementary metal oxide semiconductor Scanning electron microscopy α,α,α,α-tetraaryl-1,3-dioxolane-4,5- dimethanols Time-correlated single photon counting Trifluoroacetic acid Trifluoroacetic anhydride Tetrahydrofuran Total internal reflection fluorescence microscope Thin layer chromatography