Synthesis of chiral phosphino-sulfoximines through phospha-Michael addition and their evaluation as 1,5-P,N-ligand in asymmetric allylic alkylation [Elektronische Ressource] / vorgelegt von Fabien Lemasson

Fabien Tellier

Informations

• Publié par: rheinisch-westfalischen_technischen_hochschule_-rwth-_aachen
• Publié le: 01 janvier 2008
• Nombre de lectures: 9
• Langue: English
• Poids de l'ouvrage: 5 Mo

Extrait

Synthesis of Chiral Phosphino-Sulfoximines Through
Phospha-Michael Addition and Their Evaluation as
1,5-P,N-Ligand in Asymmetric Allylic Alkylation






Von der Fakultät für Mathematik, Informatik und Naturwissenschaften der RWTH Aachen
University zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften
genehmigte Dissertation




vorgelegt von




Master of Science

Fabien Lemasson




aus Rennes (Frankreich)







Berichter: Universitätsprofessor Dr. Ing. Hans-Joachim Gais
Universitätsprofessor Dr. rer. nat. Dieter Enders



Tag der mündlichen Prüfung: 2. Oktober 2008




Diese Dissertation ist auf den Internetseiten der Hochschulbibliothek online verfügbar.
The work presented in this thesis was carried out at the Institut für Organische Chemie der
RWTH Aachen under the supervision of Professor Dr. Hans-Joachim Gais from September
2004 to March 2008.




First of all, I would like to thank Professor Dr. Gais for giving me the opportunity to carry out
my PhD in his research group, for his excellent supervision and useful discussions. I would
like to thank Professor Dr. Dieter Enders and Professor Dr. Albrecht Salzer for their
contribution as examiners.

Furthemore I would like to thank Cornelia Vermeeren for HPLC and GC analyses, as well as
her involvement in the group. I would like to thank the personnel of the Institut für
Organische Chemie der RWTH Aachen, especially Annette Müller and Dr. Jan Runsik for
NMR measurements. Further thanks to Professor Dr. Gerhard Raabe for solving X-ray
structures and to Grünenthal for ESI-HRMS measurements.

Thanks to my labmates Adeline Adrien, Magdalena Gerencer, Dr. Prabal Banerjee, Dr. Vasily
Tsarev and Dr. Oleg Bondarev for fruitful discussions (not only about chemistry) and nice
atmosphere in the laboratory. Thanks also to my Indian friends and collegues Vijay Iska
Baskara Reddy, Rajender Akula, Saravanan Vadivelu, Vishal Mahajan and Surendra Babu
with whom I have spent funny time and who explained me many things about the Indian
culture and traditions.

I would like to thank Dr. Arun Narine for useful hints about English langage.

And finally a special thank to my friend Dr. Nicolas Lassauque who take time to read and
correct my thesis and gave me interesting suggestions.




A part of this work has already been published:

Fabien Lemasson, Hans-Joachim Gais and Gerhardt Raabe
“Synthesis of 1,5-P,N-Phosphino-Sulfoximines Through Phospha-Michael Reaction of
Alkenyl Sulfoximines and Their Evaluation as Ligands in Palladium-Catalyzed Allylic
Alkylation”
Tetrahedron Lett. 2007, 48, 8752-8756.


INDEX
‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾
A. THEORETICAL PART ......................................................................................................................... 1
1. Introduction....................................................................................................................................................... 2
1.1. Chirality....................................................................................................................................................... 2
1.2. Asymmetric Catalysis.................................................................................................................................. 5
1.2.1. Historical ............................................................................................................................................. 5
1.2.2. Asymmetric Allylic Alkylation ........................................................................................................... 8
1.3. Sulfoximines.............................................................................................................................................. 14
1.3.1. Historical ........................................................................................................................................... 14
1.3.2. Synthesis of Sulfoximines ................................................................................................................. 15
1.3.3. Sulfoximines as Ligands.................................................................................................................... 17
1.4. Phospha-Michael Addition........................................................................................................................ 19
1.4.1. Intoduction......................................................................................................................................... 19
1.4.2. Vinyl Sulfoximines as Michael Acceptor.......................................................................................... 22
1.5. Aim of the Project ..................................................................................................................................... 24
2. Acyclic Phosphino-Sulfoximines .................................................................................................................... 26
2.1. Introduction ............................................................................................................................................... 26
2.2. Synthesis of Acyclic Vinyl Sulfoximines.................................................................................................. 27
2.3. Phospha-Michael Addition of Acyclic Vinyl Sulfoximines ...................................................................... 28
2.3.1. Reactivity of Organophosphorous Compounds ................................................................................. 28
2.3.2. Phospha-Michael Addition of Vinyl Sulfoximine 58 ........................................................................ 30
2.3.3. Phospha-Michael Addition of N-Substituted Vinyl Sulfoximines..................................................... 34
2.4. Determination of the Absolute Configuration of Acyclic Phosphine Boranes.......................................... 36
2.5. Deboronation of Acyclic Phosphine Boranes............................................................................................ 40
2.6. Reactivity of Phosphine Boranes and Phosphino-Sulfoximines................................................................ 42
2.7. Acyclic Phosphino-Sulfoximines in Asymmetric Allylic Alkylation ....................................................... 44
2.7.1. Phosphino-Sulfoximine 62 in Asymmetric Allylic Alkylation.......................................................... 44
2.7.2. Solvent Variation............................................................................................................................... 44
2.7.3. Ligand to Metal Ratio, DABCO-BH and Counterion Effects .......................................................... 46 3
2.7.4. Phosphino-Sulfoximines 68, 69 and 84 88 in Asymmetric Allylic Alkylation ................................ 48
2.7.5. C-N and C-S Bond Formation ........................................................................................................... 51
2.7.6. Origin of the Selectivity for the Acyclic Phosphino-Sulfoximine Ligands ....................................... 52
2.8. Conclusion................................................................................................................................................. 53
3. Cyclic Phosphino-Sulfoximines...................................................................................................................... 54
3.1. Synthesis of Cyclic Vinyl Sulfoximines.................................................................................................... 55
3.1.1. Route A: Dehydrohalogenation ......................................................................................................... 57
3.1.2. Route B: Alpha Lithiation and Cyclization ....................................................................................... 59
3.2. Phospha-Michael Addition of Cyclic Vinyl Sulfoximines........................................................................ 61
3.3. Optimisation of the Diastereoselectivity of Phospha-Michael Addition of Cyclic Vinyl Sulfoximines ... 63
3.3.1. Diastereoselective Phospha-Michael Addition with Substrate Control ............................................. 63
3.3.2. Diastereoselective Phospha-Michael Addition Using Chiral Catalysts ............................................. 66
3.4. Determination of the Absolute Configuration of the Cyclic Phosphine Boranes ...................................... 71
3.5. Deboronation of Cyclic Phosphine Boranes.............................................................................................. 75
3.6. Cyclic Phosphino-Sulfoximines in Asymmetric Allylic Alkylation ......................................................... 76
3.6.1. rac-(E)-1,3-Diphenyl-2-propenyl Acetate as Substrate ..................................................................... 76
3.6.2. Substrate, Nucleophile and Solvent Variations ........................................................................