Theoretical studies in nucleophilic organocatalysis [Elektronische Ressource] / von Yin Wei

Yin Wei

Informations

• Publié par: ludwig-maximilians-universitat_munchen
• Publié le: 01 janvier 2009
• Nombre de lectures: 24
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

Dissertation zur Erlangung des Doktorgrades
der Fakultät für Chemie und Pharmazie
der Ludwig-Maximilians-Universität München








Theoretical Studies in Nucleophilic
Organocatalysis




Von

Yin Wei




Aus

Xinxiang, China


München 2008 Erklärung

Diese Dissertation wurde im Sinne von § 13 Abs. 3 der Promotionsordnung vom 29. Januar
1998 von Herrn Prof. Dr. Hendrik Zipse betreut.


Ehrenwörtliche Versicherung

Diese Dissertation wurde selbständig, ohne unerlaubte Hilfe erarbeitet.


München, am 02. 12. 2008







Yin Wei








Dissertation eingereicht am 02. 12. 2008

1. Gutachter: Prof. Dr. Hendrik Zipse
2. Gutachter: rbert Mayr

Mündliche Prüfung am 08.01.2009 This work was carried out from April 2005 to October 2008 under the supervision of
Professor Dr. Hendrik Zipse at the Department Chemie und Pharmazie of the Ludwig-
Maximilians-Universität, München.








The work for this thesis was encouraged and supported by a number of people to whom I
would like to express my gratitude at this point.
First of all, I would like to appreciate my supervisor Prof. Dr. Hendrik Zipse for giving me
the opportunity to do my Ph. D. in his group and his guidance in the course of scientific
research presented here. He at all times had an open ear for any questions regarding the work.
His critical comments on manuscripts and on this thesis were always instructive, stimulating,
and motivating.
I thank Prof. Dr. Herbert Mayr for agreeing to be my “Zweitgutachter”, as well as Prof. Dr.
Regina de-Vivie Riedle, Prof. Dr. Manfred Heuschmann, Prof. Dr. Rudolf Knorr and Prof.
Dr. Wolfgang Steglich for the interest shown in the present manuscript by accepting to be
referees.
I am especially indebted to Dr. G. N. Sastry for giving some “weird” but inspired
suggestions and for being a great host during my two months stay in IICT, Hyderabad, India.
I would especially like to thank my great colleague Dr. Ingmar Held who I spent the whole
Ph. D. time with, for his helps, interesting discussions and helpful suggestions.
Furthermore, I would like to thank my colleagues Boris Maryasin and Florian Achrainer for
careful corrections of the present manuscript, and other staff, post-docs and Ph. D. students
that went through my Ph. D., especially for Ms. Anna Katharina Probst, Dr. Christian
Fischer, Yinghao Liu, Evgeny Larionov for their helps and lasting friendships, which have
made my time in Germany a pleasant and worthwhile experience.
I thank DFG and Ludwig-Maximilians-Universität, München for financial support and
Leibniz-Rechenzentrum München for providing some computation facilities.
Words of special gratitude are addressed to my family, especially my parents, my brother
for their love and persistent support.
Finally, I sincerely thank my husband Xiaoyin Yang for his love, encouragement and
supporting throughout these years.–Thank you very much! Parts of this Ph. D. Thesis have been published:

1. Estimating the Stereoinductive Potential of Cinchona Alkaloids with a Prochiral Probe
Approach
Yin Wei, G. N. Sastry, Hendrik Zipse, Org. Lett. 2008, 23, 5413-5416.

2. Tautomeric Equilibria in 3-Amino-1-(2-aminoimidazol-4-yl)-prop-1-ene, a Central
Building Block of Marine Alkaloids
Yin Wei, Hendrik Zipse, Eur. J. Org. Chem. 2008, 3811-3816.

3. Methyl Cation Affinities of Commonly Used Organocatalysts
Yin Wei, G. N. Sastry, Hendrik Zipse, J. Am. Chem. Soc. 2008, 130, 3473-3477.

4. Assessment of Theoretical Methods for the Calculation of Methyl Cation Affinities
Yin Wei, Thomas Singer, Herbert Mayr, G. N. Sastry, Hendrik Zipse,
J. Comput. Chem. 2008, 29, 291-297.

5. Stacking Interactions as the Principal Design Element in Acyl-Transfer Catalysts
Yin Wei, Ingmar Held, Hendrik Zipse, Org. Biomol. Chem. 2006, 4, 4223-4230.

6. The Performance of Computational Techniques in Locating the Charge Separated
Intermediates in Organocatalytic Transformations
Yin Wei, B. Sateesh, Boris Maryasin, G. N. Sastry, Hendrik Zipse,
J. Comput. Chem. submitted.









Table of Contents

1. GENERAL INTRODUCTION .......................................................................................1
1.1 ACYLATION REACTIONS CATALYZED BY DMAP DERIVATIVES ................................................................... 1
1.2 MORITA-BAYLIS-HILLMAN REACTION.......................................................................................................... 4
1.3 OBJECTIVE AND SYNOPSIS............................................................................................................................. 6
2. METHYL CATION AFFINITY – A GENERAL DESCRIPTOR OF
ORGANOCATALYTIC REACTIVITY............................................................................8
2.1 INTRODUCTION.............................................................................................................................................. 8
2.2 ASSESSMENT OF THEORETICAL METHODS FOR CALCULATIONS OF METHYL CATION AFFINITIES ................ 9
2.2.1 Using NH and PH as Model Systems ............................................................................................ 9 3 3
2.2.2 Using Small Neutral and Anionic Nuleophiles as Model Systems ................................................. 14
2.2.3 Using Small Nitrogen- and Phosphorous-Containing Bases as Model Systems............................ 17
2.2.4 Conclusions.................................................................................................................................... 19
2.3 METHYL CATION AFFINITIES (MCAS) OF COMMONLY USED ORGANOCATALYSTS .................................... 20
2.3.1 MCA Values of Commonly Used Organocatalysts ........................................................................ 20
2.3.2 Correlation of MCA and PA Values............................................................................................... 24
2.3.3 Coon of MCA and Experimental Catalytic Rates ................................................................ 25
2.3.4 Conclusions...................... 28
3. ESTIMATING THE STEREOINDUCTIVE POTENTIAL OF CINCHONA
ALKALOIDS WITH A PROCHIRAL PROBE APPROACH ......................................29
3.1 INTRODUCTION............................................................................................................................................ 29
3.2 MOSHER’S CATION AFFINITY (MOSCA) VALUES AND MCA VALUES ........................................................ 31
3.3 CONFORMATIONAL PROPERTIES OF CINCHONA ALKALOIDS, THEIR METHYL CATION ADDUCTS AND MOSC
ADDUCTS........................... 35
3.4 CORRELATION OF MOSCA VALUES WITH OTHER PROPERTIES .................................................................. 45
3.5 CONCLUSIONS.............. 47
4. THE PERFORMANCE OF COMPUTATIONAL METHODS IN LOCATING THE
CHARGE-SEPARATED INTERMEDIATES IN ORGANOCATALYTIC
TRANSFORMATIONS .....................................................................................................48
4.1 INTRODUCTION............................................................................................................................................ 48
4.2 GEOMETRIES AND ENERGIES OF ZWITTERIONIC ADDUCTS.......................................................................... 49
4.3 THEORETICAL BENCHMARKING OF REACTION ENERGIES............................................................................ 53
4.4 EXTENSION TO LARGER SYSTEMS ............................................................................................................... 57
4.5 CONCLUSIONS.............. 59
5. CRITICAL DESIGN ELEMENTS FOR ACYL-TRANSFER CATALYSTS.........60
5.1 INTRODUCTION............................................................................................................................................ 60
5.2 FORCE FIELD DEVELOPMENT AND SELECTION OF METHODS ...................................................................... 62
5.2.1 Development of OPLS All-Atom Force Field and Conformational Search ................................... 62
5.2.2 Selection of Methods...................................................................................................................... 64
5.3 CONFORMATIONAL PROPERTIES OF ACYLPYRIDINIUM-CATIONS ................................................................ 67
5.4 REACTION ENTHALPIES FOR ACETYL GROUP TRANSFER ............................................................................ 73
5.5 CONCLUSIONS.............. 76
6. OPTIMAL SELECTIVITY OF CHIRAL ANALOGUES OF 4-
(DIMETHYLAMINO)PYRIDINE FOR NONENZYMATIC ENANTIOSELECTIVE
ACYLATIONS: A THEORETICAL INVESTIGATION..............................................77
6.1 INTRODUCTION.....................