Nucleophilicities and Lewis Basicities of Tertiary Amines

453 Pages·2010·3.22 MB·English

by  Baidya, Mahiuddin

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

Nucleophilicities and Lewis Basicities of Tertiary Amines: A Key
to Rationalize Nucleophilic Organocatalysis

M. Sc. Md. Mahiuddin Baidya
from
Karalirchack, India

München, 2009
Erklärung

Diese Dissertation wurde im Sinne von § 13 Abs. 3 bzw. 4 der Promotionsordnung vom 29.
Januar 1998 von Prof. Herbert Mayr betreut.

Ehrenwörtliche Versicherung

Diese Dissertation wurde selbständig, ohne unerlaubte Hilfe erarbeitet.

München, am …………….. ……………………………
Md. Mahiuddin Baidya

Dissertation eingereicht am 30.11.2009

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

Mündliche Prüfung am 22.12.2009

ii
...dedicated to my parents
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Acknowledgements

Productive research and educational achievement require the collaboration and support of
many people. A Ph.D. project is no exception and in fact, its building blocks are laid over the
years with the contribution of numerous persons. As I complete this thesis, bringing to a close
another chapter in my life, I wish to take this opportunity to write a few lines to express my
appreciation to the many persons who have assisted and encouraged me in this long journey.

First of all, I would like to express my deep and sincere gratitude to my supervisor, Professor
Dr. Herbert Mayr for the opportunity to work in his esteemed research group, especially for
allowing me a large degree of independence and creative freedom to explore myself.

I am grateful to Professor Dr. Hendrik Zipse who commented on my research and reviewed
the thesis.

My special thanks to Professor Dr. Sinjiro Kobayashi, Dr. Armin R. Ofial, Dr. Thanh Binh
Phan, and Dr. Sami Lakhdar for their encouragement, guidance, and helpful suggestions. I
would also like to convey my deep regards to Professor Dr. Rory M. O’Ferrall (UCD) for
allowing his precious time to read the thesis and providing his valuable suggestions.

I am grateful to all past and present members of our research group. I am privileged for
having K. Tanja, Dr. C. Saloua, A. Antipova, Dr. D. Richter, Dr. H. Schaller, N. Hampel, B.
Janker, Dr. F. Brotzel, Dr. S. Berger, Dr. M. Westermaier, Dr. F. Seeliger, Dr. O. Kaumanns,
Dr. L. Shi, M. Horn, R. Appel, M. Bregust, C. Nolte, B. Maji, N. Streidl, K. Troshin, J.
Ammer, T. Nigst, W. Han, Dr. T. Yue, Dr. X. Duan, D. Allgäuer, I. Zenz, and H. Laub as my
colleges who have provided great company during all those years in Munich. It was hardly
possible for me to thrive in my doctoral work without the precious support of these
personalities.

I express thanks Frau Dubler and Dr. Stephenson for the measurement of NMR spectra and
Dr. P. Mayer for solving crystal structures.

I am very obliged to Frau H. Lipfert for helping me out from various academic and non-
academic constrains which made my stay commodious from the very beginning till now in
this city.

I wish to thank my friends from Munich and rest of the world for their suggestions and co-
operations.

Finally, I am forever indebted to my parents, sisters, and my whole family for their endless
patience, constant long-distance support, personal inspiration, and so much more that I can
not explain here.

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Part of this Dissertation have been published in:

DABCO or DMAP – Why Are They Different in Organocatalysis?
M. Baidya, S. Kobayashi, F. Brotzel, U. Schmidhammer, E. Riedle, H. Mayr,
Angew. Chem. 2007, 119, 6288-6292; Angew. Chem. Int. Ed. 2007, 46, 6176.

Nucleophilicities and Carbon Basicities of DBU and DBN
M. Baidya, H. Mayr, Chem. Commun. 2008, 1792-1794.

Organocatalytic Activity of Cinchona Alkaloids: Which Nitrogen is More Nucleophilic?
M. Baidya, M. Horn, H. Zipse, H. Mayr, J.Org. Chem. 2009, 74, 7157-7164.

S 2’ versus S 2 Reactivity: Control of Regioselectivity in Conversions of Baylis- Hillman
N N
Adducts
M. Baidya, G. Remennikov, P. Mayr, H. Mayr, Chem. –Eur. J. 2009, in print.

Nucleophilicities and Lewis Basicities of Imidazoles, Benzimidazoles, and Benzotriazoles
M. Baidya, F. Brotzel, H. Mayr, Org. Biomol. Chem. 2009, submitted.

Nucleophilicity and Nucleofugality of Phenylsulfinate (PhSO –): A Key to
2
Understanding its Ambident Reactivity
M. Baidya, S. Kobayashi, H. Mayr, J. Am. Chem. Soc. 2009, submitted.

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Conferences and Meeting Attended

Nucleophilicities and Lewis Basicities of Organocatalysts
Poster presentation in 19th IUPAC conference on Physical Organic Chemistry, 2008, Spain.

Nucleophilicities and Lewis Basicities of Tertiary Amines: A Key to Rationalize
Nucleophilic Organocatalysis
Poster presentation in International Symposium on Modern Organic Chemistry (ISMOC),
2009, Tunisia.

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Table of Contents

0. Summary 1

1. Introduction 15

2. DABCO and DMAP – Why are They Different in Organocatalysis? 33

Introduction 33
Results and Discussion 35
Conclusion 41
References 41
Experimental Section 44

3. Does Low Nucleophilicity Limit the Use of DBU and DBN as Organocatalysts? 64

Introduction 64
Results and Discussion 65
Conclusion 70
References 71
Experimental Section 73

4. Organocatalytic Activity of Cinchona Alkaloids: Which Nitrogen 94
is More Nucleophilic?

Introduction 94
Results 95
Discussion 101
Conclusion 117
References 117
Experimental Section 112

5. Nucleophilicities and Lewis Basicities of Imidazoles, Benzimidazoles, 137
and Benzotriazoles

Introduction 137
Results and Discussion 139
Conclusion 152
References 153
Experimental Section 157

6. S 2’ versus S 2 Reactivity: Control of Regioselectivity in Conversions of 198
N N
Baylis-Hillman Adducts

Introduction 198
Results 200
Discussion 209
Conclusion 210
References 212
Experimental Section 215
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7. Nucleophilicity and Nucleofugality of Phenylsulfinate (PhSO –): A Key to 240
2
Understanding its Ambident Reactivity

Introduction 240
Results 243
Discussion 254
Conclusion 262
References 263
Experimental Section 267

8. Benzhydrylium ions: A Versatile Tool for Determining Carbon Basicities 315

Introduction 315
Method 316
Results and Discussion 317
Conclusion 335
References 336
Experimental Section 337

9. Miscellaneous Experiments 397

Nucleophilic Reactivities of 5-Phenyltetrazole, Pyrazole, Oxazole, and Thiazole 397
Nucleophilicity and Carbon Basicity of Isoquinoline 400
Nucleophilicities of Aliphatic Tertiary Amines 402
References 410
Experimental Section 412

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List of Abbreviations

aq. aqueous
Bu butyl
calc. calculated
DMSO dimethyl sulfoxide
d doublet
exp. experimental
eq. equivalent(s)
ee enatiomaric excess
Et ethyl
EtOAc ethyl acetate
et al. et alii
E electrophilicity parameter
h hour(s)
i.e. id est
k rate constant
K equilibrium constnat
M mol L–1
min minute(s)
Me Methyl
N nucleophilicity parameter
NMR nuclear magnatic resonance
mp melting point
Ph phenyl
q quartet
ref. reference
r.t. room temperature
s nucleophile specific slope parameter
s singlet
t triplet
UV ultra violet
Vis visible
vs. versus
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Chapter 0 : Summary
Chapter 0

Summary

0.1 General

Benzhydrylium ions (Ar CH+) and structurally related quinone methides are employed as
2
reference electrophiles for comparing the nucleophilicities of a large variety of compounds,
e.g., alkenes, arenes, alkynes, allylsilanes, allylstannanes, enol ethers, enamines, diazo
compounds, carbanions, transition-metal π-complexes, hydride donors, phosphanes, amines,
alkoxides, etc., using the linear-free-energy relationship (eq 1), where s and N are
nucleophile-specific parameters and E is an electrophile-specific parameter.

log k (20 °C) = s(N + E) (1)

The same equation was employed to derive the electrophilicity parameter E for different types
of carbocations, cationic transition-metal π-complexes, typical Michael acceptors, iminium
ions, and electron-deficient arenes. The E, N, and s parameters thus obtained have been used
for predicting rates and selectivities of polar organic reactions.

0.2 DABCO and DMAP–Why Are They Different in Organocatalysis?

Rate and equilibrium constants (k and K) for the reactions of 1,4-diazabicyclo[2.2.2]octane
(DABCO), quinuclidine, and 4-(dimethylamino)pyridine (DMAP, Steglich’s base) with
benzhydrylium ions (Ar CH+) have been determined spectrophotometrically in acetonitrile at
2
20 °C (Scheme 1).
Ar k Ar H
H + :NR
3 NR
Ar k-1 Ar 3
K = k / k
-1
:NR3 = N N N N NMe2
DABCO Quinuclidine DMAP

Scheme 1. Reactions of benzhydrylium ions with tertiary amines.

It is demonstrated that the bicyclic amines DABCO and quinuclidine are 103 times better
nucleophiles than DMAP (Figure 1), but at the same time 106-105 times better nucleofuges.
1