Asymmetric synthesis of medium-sized carbocycles, spirocycles and oxabicycles via ring closing metathesis of sulfoximine substituted trienes and dihydropyran derivatives [Elektronische Ressource] / vorgelegt von Michal Lejkowski

Schneider Electric

Informations

• Publié par: rheinisch-westfalischen_technischen_hochschule_-rwth-_aachen
• Publié le: 01 janvier 2008
• Nombre de lectures: 16
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

Asymmetric Synthesis of Medium-Sized Carbocycles,
Spirocycles and Oxabicycles via Ring-Closing Metathesis of
Sulfoximine-Substituted Trienes and Dihydropyran
Derivatives

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
Michal Lejkowski


aus Lodz (Polen)



Berichter: Universitätsprofessor Dr. Ing. Hans-Joachim Gais

Universitätsprofessor Dr. rer. nat. Dieter Enders

Tag der mündlichen Prüfung: 06. November 2008


Diese Dissertation ist auf den Internetseiten der Hochschulbibliothek online verfügbar.












For Magda,
for my parents


















The work presented in this thesis was carried out at the Institute of Organic Chemistry of
the RWTH-Aachen University, under the supervision of Prof. Dr. Hans-Joachim Gais
between February 2005 and February 2008.

I would like to thank Prof. Dr. Hans-Joachim Gais for giving me the opportunity to work
on this exciting research topics, excellent conditions and support in his research group. I
would also like to thank Prof. Dr. Hans-Joachim Gais for his inspiring guidance,
encouragement and providing inordinate freedom in my lab. Working with him has been
a great and memorable experience.















It is my great pleasure to extend my heartfelt thanks to all my colleagues. I thank all the
non-teaching staff of the Department and particularly I would like to thank Mrs. C.
Vermeeren, Mr. B. Sommer and Mrs. Gerencer for their support.



Parts of this work have already been published:

Asymmetric Synthesis of Spiroketal, Spiroether, and Oxabicycle Building Blocks via
Stereoselective Spiro- and Bicycloannulation of 2-Hydroxy Dihydropyrans,
Lejkowski, M.; Banerjee, P.; Runsink, J.; Gais, H.-J. Org. Lett. 2008; 10, 2713

Asymmetric Modular Synthesis of Highly Functionalized Medium-Sized Carbocycles
and Lactones via Ring-Closing Metathesis of Sulfoximine-Substituted Trienes ;
Lejkowski; M.; Gais, H.-J.; Banerjee, P.; Vermeeren, C. J. Am. Chem. Soc. 2006, 128,
15378





















CONTENTS
Contents
Theoretical Part
1. General introduction: sulfoximine chemistry...............................................1
2. Asymmetric synthesis of functionalized carbocycles via Ring-Closing
Metathesis of sulfoximine-substituted trienes…………….……………….…5
2.1 Introduction: RCM.............................................…………………………..5
2.2 Project objectives.............................................……………………………12
2.3 Synthesis of allylic sulfoximines via AEI route………………………….17
2.4. Synthesis of sulfoximine substituted homoallylic alcohols.………..…..18
2.4.1 Synthesis of sulfoximine substituted silyl ethers……………..…..23
2.5 Synthesis of sulfoximine substituted trienes……………………………..24
2.5.1 Introduction.......................................................................................24
2.5.2 Synthesis of trienes via α -alkylation of alkenyl sulfoximines…...26
2.5.3 Synthesis of trienes via α-hydroxyalkylation of alkenyl
sulfoximines……………………………………………...………...28
2.5.4 Synthesis of trienes via addition of Grignard reagents to the α -
sulfoximido aldehydes…………………………………………….31
2.5.5 Synthesis of trienes via addition of Grignard reagents to the α-
sulfoximido ketones……………………………………………….34
2.5.5.1. Oxidation of sulfoximine substituted allylic alcohols…..35
2.5.5.2. Addition of Grignard reagents to
α-sulfoximido ketones………………………………………...…...38
2.6. RCM of sulfoximine substituted trienes………………………………...40
2.6.1 Introduction………………………………………………………...40
2.6.2 Results and discussion…………………………………………..…45
CONTENTS
2.6.3 Determination of conformation of representative cyclic allylic
alcohols S-139, R-139 and R-Z-140…………………………………...…60
2.7. Transformations of sulfoximine-substituted carbocycles.
2.7.1 Selective desilylation–oxidation of sulfoximine-substituted cyclic
allylic alcohols……………………………………………………………62
2.8 Replacement of the sulfoximine group……….………………………….64
2.8.1 Copper mediated Cross-coupling…………………………………68
2.8.2. Reductive cleavage…………………………………...……………69
2.9 Summary…………………………………………………………..………72
3. Asymmetric synthesis of functionalised oxabicycles, spiroethers and spiroketals
using Ring-Closing Metathesis protocol and Prins reaction of sulfoximine-
substituted pyran derivatives………………….……………………………..77
3.1 Introduction: Pyrans, oxabicycles, spiroethers and spiroketals…….....77
3.2 Project objectives.........................................................................……........83
3.3 Synthesis of sulfoximine-substituted pyran derivatives………………...86
3.4 Synthesis of sulfoximine-substituted oxabicycles………………...……...94
3.5 Synthesis of sulfoximine-substituted spiroethers……….……………...100
3.5.1. The Prins reaction – introduction………….……..……….…….101
3.6 Synthesis of sulfoximine-substituted spiroketals…………………….…111
3.7 Replacement of the sulfoximine moiety…………………………….…...117
3.8 Summary.....................................................................................................121
4. Experimental Part………..…………………………………………….….125
4.1 General Remarks…………………………………………………………126
4.2 Determination of the Physical Data……………………………………..126
4.3 Reagents and solvents……………………………………………………129
4.4. Synthesis of Sulfoximine-Substituted Homoallylic Alcohols ………....131 CONTENTS
4.4.1 General Procedure for the Synthesis of Homoallylic Alcohols 74, 75 and 76
(GP1)……………………………………………………………………………………..….131
4.4.2 Synthesis of (1Z,3R,4S,5E)-3-Isopropyl-1-[(S)-N-methyl-S-phenyl-sulfonimidoyl)]-
hepta-1,5-dien-4-ol (74)……………………………………………………………………131
4.4.3 Synthesis of (Z,3R,4S)-3-Isopropyl-1-[(S)-N-methyl-S-phenyl-sulfonimidoyl)]octa-1,7-
dien-4-ol (75)..……………………………………...……………………………………….132
4.4.4 Synthesis of (S,E)-1-((R,Z)-2-[(S)-N-methyl-S-phenyl-sulfonimidoyl)]-cyclohexyl)but-
2-en-1 (76)..………………………….………………………………..…………………….134
4.5. Synthesis of Sulfoximine-Substituted Silyl Ethers…………………………136
4.5.1 General Procedure for the Synthesis of the Silyl Ethers 77 79 (GP2)………..…..136
4.5.2 Synthesis of triethyl-((1Z,3R,4S,5E)-3-isopropyl-1-[(S)-N-methyl-S-phenyl-
sulfonimidoyl)]-hepta-1,5-dien-4-yloxy)silane (77)…………….…………………………136
4.5.3 Synthesis of ((Z,3R,4S)-3-Isopropyl-1-[(S)-N-methyl-S-phenyl-sulfonimidoyl)]octa-1,7-
dien-4-yloxy)triethylsilane (78)………………………...…….137
4.5.4 Synthesis of triethyl-((S,E)-1-((R,Z)-2-[(S)-N-methyl-S-phenyl-
sulfonimidoyl)]cyclohexyl)but-2-enyloxy)silane (79)………………………...…………...139
4.6 Synthesis of Sulfoximine-Substituted Trienes…………….…………………141
4.6.1 General Procedure for the Synthesis of Trienes 84 and 85
(GP3)………………………………………………………………………………………...141
4.6.2 Synthesis of triethyl((2E,4S,5R,6E)-5-isopropyl-7-[(S)-N-methyl-S-phenyl-
sulfonimidoyl)]-deca-2,6,9-trien-4-yloxy)silane (84)…………...……………………...…141
4.6.3 (Synthesis of (E,5S,6R)-6-Isopropyl-8-[(S)-N-methyl-S-phenyl-sulfonimidoyl)]undeca-
1,7,10-trien-5-yloxy)triethylsilane (85)……………………………………………………142
4.6.4 Attempted synthesis of triethyl-((2E,4S,5R,6E)-5-isopropyl-7-[(S)-N-methyl-S-phenyl-
sulfonimidoyl)]undeca-2,6,10-trien-4-yloxy)silane (86)…………………………….……144
4.6.5 Attempted synthesis of triethyl-((2E,4S,5R,6E)-5-isopropyl-7-[(S)-N-methyl-S-phenyl-
sulfonimidoyl)]dodeca-2,6,11-trien-4-yloxy)silane (87)………………………………….145
4.6.6 Attempt to synthesis of triethyl((5S,6R,E)-6-isopropyl-8-[(S)-N-methyl-S-phenyl-
sulfon-imidoyl)]trideca-1,7,12-trien-5-yloxy)silane (88)…………………………………146
4.7. Synthesis of Trienes via α-Hydroxyalkylation of Alkenyl Sulfoximines.....147
4.7.1 General Procedure for the Synthesis of Allylic Alcohols (GP 4)…….…….………147
----CONTENTS
4.7.2 Synthesis of (2E,4S,5E,7R,8S,9E)- and (2E,4S,5E,7R,8S,9E)-7-isopropyl-5-[(S)-N-
methyl-S-phenyl-sulfonimidoyl)]8-(triethylsilyloxy)undeca-2,5,9-trien-4-ol (R-89) and (S-
89).........................................................................................................................................147
4.7.3 Synthesis of (5R,6E,8R,9S,10E)- and (5S,6E,8R,9S,10E)-8-isopropyl-6-[(S)-N-methyl-
S-phenyl-sulfonimidoyl)]-9-(triethylsilyloxy)dodeca-1,6,10-trien-5-ol (R-90) and (S-
90).........................................................................................................................................149
4.7.4 Synthesis of (7R,8E,10R,11S,12E)- and (7S,8E,10R,11S,12E)-10-isopropyl-8-[(S)-N-
methyl-S-phenyl-sulfonimidoyl)]-11-(triethylsilyloxy)tetradeca-1,8,12-trien-7-ol (R-91) and
(S-91)....................................................................................................................................152
4.7.5 Synthesis of (5R,8R,9S,E)- and (5S,8R,9S,E)-8-Isopropyl-6-[(S)-N-me