Novel aza-arylphosphane ligands for ruthenium catalyzed anti Markovnikov hydration of terminal alkynes [Elektronische Ressource] / vorgelegt von Aurélie Labonne

Aurel Stein

Informations

• Publié par: rheinisch-westfalischen_technischen_hochschule_-rwth-_aachen
• Publié le: 01 janvier 2007
• Nombre de lectures: 9
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

Novel Aza-Arylphosphane Ligands
For Ruthenium-Catalyzed
Anti-MARKOVNIKOV Hydration of Terminal Alkynes



Von der Fakultät für Mathematik, Informatik und Naturwissenschaften der Rheinisch-
Westfälischen Technischen Hochschule Aachen zur Erlangung des akademischen Grades einer
Doktorin der Naturwissenschaften
genehmigte Dissertation


vorgelegt von


Master of Science
Aurélie Labonne


aus Paris (France)



Berichter: Universitätprofessor Dr. C. Bolm
Universitätprofessor Dr. D. Enders



Tag der mündlichen Prüfung: 06. Juli 2007


Diese Dissertation ist auf den Internetseiten der Hochschulbibliotek
online verfügbar.

The work presented in this thesis was carried out at the Institute of Organic Chemistry of
RWTH Aachen University between January 2004 and January 2007 under the supervision of
Dr. Lukas Hintermann.

I would like to thank Dr. Lukas Hintermann for giving me the opportunity to work on this
exciting research theme and for the useful discussions. I would also thank Prof. Dr. Carsten
Bolm for his parallel constant support.
I would like to thank Prof. Dr. Dieter Enders for his kind assumption of the co-reference.






Parts of this work have already been published:

1) A. Labonne, T. Kribber, L. Hintermann
“Highly Active in Situ Catalysts for anti-Markovnikov Hydration of Terminal
Alkynes”
Org. Lett. 2006, 8, 5853-5856.

2) L. Hintermann, A. Labonne
“Catalytic Hydration of Alkynes and its Aplication in Synthesis”
Synthesis 2007, 1121-1150.

3) T. Kribber, A. Labonne, L. Hintermann
“Iterative Synthesis of Oligo-1,4-Diols via Catalytic anti-Markovnikov Hydration of
Terminal Alkynes”
Synthesis 2007, in press.

4) A. Labonne, L. Zani, L. Hintermann, C. Bolm
“Redox-neutral Synthesis of β-Amino Aldehydes from Imines by an
Alkynylation/Hydration Sequence”
J. Org. Chem. 2007, 72, 5704-5708.








« Nothing in life is to be feared, it is only to be understood »

Marie Sklodowska-Curie








« Que serais-je sans toi qui vins à ma rencontre
Que serais-je sans toi qu'un coeur au bois dormant
Que cette heure arrêtée au cadran de la montre ue ce balbutiement… »

Louis Aragon, poem « Que serais-je sans toi »







Table of Contents

1. Introduction ------------------------------------------------------------------------------------------------------ 1
2. Catalytic Hydration of Alkynes------------------------------------------------------------------------------ 7
2.1 Markovnikov Hydration of Alkynes---------------------------------------------------- - 10 -
2.1.1. Mercury, BRØNSTED-Acid and -Base Catalysts------------------------------------ - 10 -
2.1.1.1. Mercury Catalysts ---------------------------------------------------------------- - 10 -
2.1.1.1. Brønsted-Acid and -Base Catalysts -------------------------------------------- - 13 -
2.1.2. Non-Mercurial Catalysts for Alkyne Hydration ---------------------------------------16
2.1.2.1. Zinc, Cadmium, Tellurium, Thallium----------------------------------------------16
2.1.2.2. Groups 1 Through 7 and Lanthanides----------------------------------------------17
2.1.2.3. Iron, Ruthenium and Osmium (Group 8)------------------------------------------17
2.1.2.4. Rhodium and Iridium (Group 9)------------------------------------------------ - 20 -
2.1.2.5. Palladium, Platinum (Group 10) - 22 -
2.1.2.6. Copper, Silver, Gold (Group 11) ----------------------------------------------- - 25 -
2.2 Anti-MARKOVNIKOV Hydration of Terminal Alkynes ----------------------------------29
2.2.1. Ruthenium-catalyzed Anti-MARKOVNIKOV Hydration -------------------------------29
2.2.2. Mechanism of Ruthenium-catalyzed Anti-MARKOVNIKOV Hydration of Terminal
Alkynes ----------------------------------------------------------------------------------------- - 33 -
2.2.3. Substrate Range of Anti-MARKOVNIKOV Hydration of Terminal Alkynes---------36
3. Aims of the Project----------------------------------------------------------------------------------------- 37 -
4. Synthesis of Aza-Arylphosphanes--------------------------------------------------------------------- 38 -
4.1. Preparation of 2-Pyridylphosphanes via a WITTIG-Olefination/Cyclization
Strategy -----------------------------------------------------------------------------------------------39
4.2. Preparation of 2-Substituted Aza-Arylphosphanes via Cross-
Coupling/Nucleophilic Substitution Strategy---------------------------------------------- - 42 -
4.2.1 Synthesis of 2-Substituted Aza-Arylphosphanes: A →B-Sequence-------------- - 44 -
4.2.1.1 Phosphination of 2,6-Dichloropyridine----------------------------------------- - 44 -
4.2.1.2 Cross-Coupling Reactions of 2-Chloro-6-(diphenylphosphino)pyridine with
Alkyl Sources -----------------------------------------------------------------------------------45
4.2.1.3. Nucleophilic Substitution with Alcoholates---------------------------------------46
4.2.2 Synthesis of 6-Substituted Aza-Arylphosphanes: B →A-Sequence-------------- - 47 -
4.2.2.1 Cross-Coupling of 2,6-Dichloro-Aza-Aryls with Alkyl Grignard-Reagents --47
Table of Contents

4.2.2.2 Cross-Coupling of 2,6-Dichloro-Aza-Aryls with Aryl Grignards-Reagents - 53
-
4.2.2.3 Phosphination of 2-Substituted 6-Chloro-Aza-Aryl Compounds ---------------58
5. [CpRu(L) CH CN]PF Complexes --------------------------------------------------------------------- 62 - 2 3 6
5.1. Preparation of Complexes [CpRu(L) CH CN]PF ---------------------------------- - 62 - 2 3 6
5.2. Ligand Effect on the Ru-Catalysed Hydration Reaction of Terminal Alkynes - 73 -
6. Ruthenium-catalyzed Hydration of Terminal Alkynes--------------------------------------------- 82 -
6.1. Hydration of Propargylalcohols -------------------------------------------------------- - 82 -
6.2. Use of Catalysts [CpRu(L) CH CN]PF in the Hydration of Terminal Alkynes--86 2 3 6
6.3. Synthesis of β-Amino Aldehydes -----------------------------------------------------------89
6.3.1.1. Hydration of N-Protected Propargylic Amines ------------------------------- - 94 -
6.3.1.2. Hydration of N-Protected Propargylic Amines under Microwave Irradiation---
97 -
6.3.2. Synthesis of rac-β-Amino Acids---------------------------------------------------- - 101 -
6.3.3. Synthesis of rac-1,3-Amino Alcohols---------------------------------------------- - 102 -
7. Summary and Outlook--------------------------------------------------------------------------------- - 104 -
8. Experimental Section ---------------------------------------------------------------------------------- - 108 -
8.1. General Remarks ------------------------------------------------------------------------- - 108 -
8.1.1. Solvents -------------------------------------------------------------------------------- - 108 -
8.1.2. Chemicals------------------------------------------------------------------------------ - 109 -
8.1.3. Analytics Methods-------------------------------------------------------------------- - 109 -
8.1.4. Chromatography ---------------------------------------------------------------------- - 111 -
8.1.5. Compounds Prepared Following Literature Procedures ------------------------- - 111 -
8.1.6. Microwave-assisted Reactions ------------------------------------------------------ - 111 -
8.2. General Synthetic Procedures---------------------------------------------------------- - 112 -
8.3. Synthesis of Pyridin-2(1H)-one Derivatives ----------------------------------------- - 118 -
8.4. Synthesis of Chloro-substituted Aza-aryl Derivatives----------------------------- - 121 -
8.5. Synthesis of Pyridylphosphane Derivatives - 123 -
8.6. Synthesis of Aza-alkoxyphosphanes 142a/b - 125 -
Table of Contents

8.7. Synthesis of Alkyl-substituted Aza-aryl Derivatives------------------------------- - 127 -
8.8. Synthesis of 2-Halo-6-arylpyridines--------------------------------------------------- - 134 -
8.9. Synthesis of Aza-alkylphosphanes 130a-f, 158-------------------------------------- - 142 -
8.10. Synthesis of Aza-arylphosphanes 130g-o ------------------------------------------- - 147 -
58.11. Synthesis of [η -cyclopentadienylruthenium(II) bis-aza-
arylphosphane(acetonitrile)][Counterion] ------------------------------------------------ - 156 -
8.12. Synthesis of Propargylalcohols 171 and Derivatives ----------------------------- - 164 -
8.13. Synthesis of Aldehydes 177/179 ------------------------------------------------------ - 168 -
8.14. Synthesis of N-Tosyl-1-amino-1-propanal Derivatives 208a-i ------------------ - 173 -
8.15. Synthesis of N-Tosyl-β-amino-acid Derivatives ----------------------------------- - 180 -
8.16. Synthesis of N-Tosyl-β-amino-alcohol Derivatives ------------------------------- - 181 -
9. Appendix -------------------------------------------------------------------------------------------------- - 185 -
9.1. List of Abbreviations-----------------