Asymmetric anhydride opening: optimization and applications [Elektronische Ressource] / vorgelegt von Iuliana Luisa Atodiresei (geborene Ghilan)

Atodiresei Nicolae

Informations

• Publié par: rheinisch-westfalischen_technischen_hochschule_-rwth-_aachen
• Publié le: 01 janvier 2005
• Nombre de lectures: 26
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

Asymmetric Anhydride Opening:
Optimization and Applications







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


Iuliana Luisa Atodiresei (geborene Ghilan)

(MASTER OF SCIENCE)

aus Radauti (Romania)





Berichter: Universitätsprofessor Dr. C. Bolm

Universitätsprofessor Dr. D. Enders





Tag der mündlichen Prüfung: 30. Mai 2005


Diese Dissertation ist auf den Internetseiten der Hochschulbibliothek online
verfügbar.

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. Carsten
Bolm between October 2001 and March 2005.





I would like to thank Prof. Dr. C. Bolm for giving me the opportunity to work on an
exciting research topic, excellent conditions, and support.
I would like to thank Prof. Dr. D. Enders for his kind assumption of the co-reference.



















Parts of this work have already been published or submitted:

Bolm, C.; Schiffers, I.; Atodiresei, I.; Ozcubukcu, S.; Raabe, G. New J. Chem. 2003,
27, 14.

Bolm, C.; Schiffers, I.; Atodiresei, I.; Hackenberger, C. P. R. Tetrahedron: Asymmetry
2003, 14, 3455.

Bolm, C.; Atodiresei, I.; Schiffers, I. Org. Synth. 2005, in press.





Table of contents
1 Introduction......................................................................................1
1.1 Proline.................................................................................................3
1.2 Amino acid derivatives ...................................................................... 9
1.2.1 Imidazolidinone derivatives ................................................................... 9
1.2.2 Peptide-based catalysts 14
1.3 Cinchona alkaloids...........................................................................17
1.3.1 Carbon-carbon bond formation ........................................................... 18
1.3.1.1 Alkylation reactions ...................................................................... 18
1.3.1.2 Aldol condensation....................................................................... 23
1.3.1.3 Michael addition 23
1.3.1.4 Baylis-Hillman reactions............................................................... 27
1.3.1.5 Asymmetric cyanation of ketones ................................................ 31
1.3.1.6 Cyclopropanation ......................................................................... 33
1.3.1.7 [2+2] Cycloaddition reactions....................................................... 34
1.3.2 Carbon-oxygen bond formation........................................................... 38
1.3.2.1 Epoxidation .................................................................................. 38
1.3.2.2 Asymmetric dihydroxylation ......................................................... 39
1.3.3 C-N bond formation............................................................................. 44
1.3.4 C-S bond formation 46
1.3.5 C-F bond formation 47
1.4 Asymmetric anhydride opening...................................................... 50
1.4.1 Chiral nucleophiles.............................................................................. 51
1.4.2 Enantioselective desymmetrization using chiral Lewis acids .............. 52
1.4.3 Enantioselective desymmetrization with chiral Lewis bases ............... 56
1.4.4 Mechanistic studies............................................................................. 62
2 Aim of the project...........................................................................63
3 Results and discussions ...............................................................64
3.1 Asymmetric anhydride opening...................................................... 64
3.1.1 Investigation of different nucleophiles ................................................. 64
3.1.2 Variation of the substrate .................................................................... 66
3.1.3 Investigation of the solvent system ..................................................... 70
3.1.4 Reaction scale-up ............................................................................... 71
Table of contents
3.2 Synthesis of β-amino acids............................................................. 72
3.2.1 Preparation of N-Cbz protected amino acid benzyl esters .................. 73
3.2.2 Synthesis of the free β-amino acids .................................................... 75
3.3 Chiral bisoxazolines.........................................................................77
3.3.1 C -symmetric chiral bisoxazolines....................................................... 79 2
3.3.2 Cbisoxazolines 83 1
3.3.3 Application in catalysis ........................................................................ 90
3.4 Chiral 1,2-diamines..........................................................................96
4 Summary and outlook...................................................................99
5 Experimental section103
5.1 General methods and chemicals ..................................................103
5.1.1 Inert atmosphere conditions...............................................................103
5.1.2 Solvents .............................................................................................103
5.1.3 Determination of the physical data.....................................................104
5.1.4 Chromatography ................................................................................106
5.1.5 Compounds synthesized according to literature procedures..............107
5.2 Asymmetric anhydride opening....................................................109
5.2.1 General procedure for the alkaloid-mediated ring opening of cyclic
meso-anhydrides (GP-1)....................................................................109
5.2.2 (2R,3S)-3-endo-Ethoxycarbonyl-bicyclo[2.2.1]hept-5-ene-2-endo-
carboxylic acid (184) ..........................................................................110
5.2.3 3-endo-(2’,2’,2’-Trifluorethoxycarbonyl)-bicyclo[2.2.1]hept-5-ene-2-
endo-carboxylic acid (185) .................................................................111
5.2.4 (2R,3S)-3-endo-Allyloxycarbonyl-bicyclo[2.2.1]hept-5-ene-2-endo-
carboxylic acid (186) ..........................................................................112
5.2.5 (2R,3S)-3-endo-Propargyloxycarbonyl-bicyclo[2.2.1]hept-5-ene-2-
endo-carboxylic acid (187) .................................................................113
5.2.6 (2R,3S)-3-endo-Benzyloxycarbonyl-bicyclo[2.2.1]hept-5-ene-2-
endo-carboxylic acid (188) .................................................................114
5.2.7 (2S,3R)-3-endo
endo-carboxylic acid (ent-188)...........................................................114
Table of contents
5.2.8 (2R,3S)-3-endo-(4-Methoxy-benzyloxycarbonyl)-bicyclo[2.2.1]hept-
5-ene-2-endo-carboxylic acid (189)....................................................115
5.2.9 (1S,2R)-cis-2-Benzyloxycarbonyl-3,3-dimethylcyclopropane-1-
carboxylic acid (190) ..........................................................................116
5.2.10 (1R,2S)-cis-2-Benzyloxycarbonyl-3,3-dimethylcyclo-propane-1-
carboxylic acid (ent-190) ....................................................................116
5.2.11 (1R,2S)-cis-2-Benzyloxycarbonyl-cyclobutane-1-carboxylic acid
(192)...................................................................................................117
5.2.12 (1S,2R)-cis-2-Benzyloxycarbonyl-cyclobutane-1-carboxylic acid
(ent-192) ............................................................................................118
5.2.13 (1R,2S)-cis-2-Benzyloxycarbonyl-cyclopentane-1-carboxylic acid
(193)...................................................................................................118
5.2.14 (1S,2R)-cis
(ent-193) ............................................................................................119
5.2.15 (1R,2S)-cis-2-Benzyloxycarbonyl-4,4-dimethylcyclo-pentane-1-
carboxylic acid (195) ..........................................................................119
5.2.16 (1S,2R)-cis
carboxylic acid (ent-195) ....................................................................120
5.2.17 (1R,2S)-cis-2-Benzyloxycarbonyl-cyclohexane-1-carboxylic acid
(196)...................................................................................................120
5.2.18 (1S,2R)-cis-2-Benzyloxycarbonyl-cyclohexane-1-carboxylic acid
(ent-196) ............................................................................................121
5.2.19 (1R,2S)-cis-2-Benzyloxycarbonyl-cyclohex-4-ene-1-carboxylic
ac