N-containing Fluorous Ligands for Aerobic Oxidations in Fluorous Biphasic Systems

154 Pages·2003·0.58 MB·English

by  Ragagnin, Gianna

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

N-containing Fluorous Ligands for
Aerobic Oxidations in Fluorous Biphasic Systems

Gianna Ragagnin

aus

Conegliano, Italien

München, 2003
Erklärung

Diese Dissertation wurde im Sinne von § 13 Abs. 3 bzw. 4 der Promotionsordnung vom 29.
Januar 1998 von Professor Dr. Paul Knochel betreut.

Ehrenwörtliche Versicherung

Diese Dissertation wurde selbständig, ohne unerlaubte Hilfe erarbeitet.

München, am 22. September 2003

Gianna Ragagnin

Dissertation eingereicht am 22. September 2003

1. Gutachter: Prof. Dr. Paul Knochel
2. Gutachter: Prof. Dr. Heinz Langhals

Mündliche Prüfung am 27. Oktober 2003
This work was carried out from June 2000 to July 2003 under the supervision of Professor
Paul Knochel at the Fakültat für Chemie und Pharmazie, Ludwig-Maximilians-Universität,

Munich.

I thank Prof. Paul Knochel for giving me the opportunity to do my Ph.D. in his group and for
the stimulating and motivating scientific discussions during this time.

I would like to thank Prof. Langhals for agreeing to be my “ Zweitgutachter”, as well as Prof.
Karaghiosoff, Prof. Lindel and Prof. Zipse for the interest shown in this manuscript by
accepting to be referees.

Helena Leuser and Andrei Gavriouchine I thank for the careful correction of the manuscript.

The European Union (contract HPRN-CT-2000-00002, “Development of Fluorous Phase
Technologies for Oxidation Processes”) is acknowlegded for financial support.

Für die tatkräftige Unterstützung im Labor bedanke ich mich bei Vladimir Malakhov und
Krystyna Becker. Gabi Fried und Beatrix Cammelade bin ich besonders dankbar für die
tägliche, nervenaufreibende administrative Unterstützung.

I would like to thank Juliette Sirieux and Henri Houte, as well as my F-Praktikantin Helen
Müller for their precious help with chemistry and the friendly working atmosphere.

I thank the whole group of Prof. Steglich for their friendly hospitality at the 4th floor during
the last year, as well as my labmates in the (ex-)lab F 2.012 Wolfgang "Meister" Dohle,
Jannis Sapountzis, Anne Eeg Jensen+Kolja Knapp, Florence Volant, Anne Staubitz and Felix
Kopp.

Furthermore, I would like to thank everyone I met during these years in this group, who made
my stay in München an unforgettable experience, through their sympathy, help, support and
friendship, and a great international atmosphere. Special thanks go to "Profésor" Jesus Angel
Varela Carrete (…it is something wonderful to have "Jesus" as a friend!!), Yasunari
Monguchi, Gabi Fried and Helena Leuser.

Infine, un ringraziamento speciale alla "Dottoressa" Claudia Piazza e a Stefano, per essermi
stati accanto con il loro affetto, da vicino o da lontano, in tutti i momenti belli o difficili di
questa avventura teutonica. Queste amicizie valgono molto, molto di piú di qualunque
risultato scientifico.
Papers related to this thesis work:

Contribution to e-eros (Electronic Encyclopedia of Reagents for Organic Synthesis
-
[Potassium
tris(1,1,1,2,2,3,3,4,4,5,5,6,6,7,7,11,11,12,12,13,13,14,14,15,15,16,16,17,17,17,-
triacontafluoro-(8,10-heptadecanedionato ) rhutenate], 2001.

G. Ragagnin, B.Betzemeier, S.Quici, P.Knochel “Copper catalyzed aerobic oxidation
-
of alcohols using fluorous biphasic catalysis” Tetrahedron 2002, 58, 3985-3991.

Ragagnin Gianna and Paul Knochel “New Fluorous benzimidazolic Ligands for
-
aerobic Ru-Catalyzed Epoxidations in Fluorous Biphase System”, manuscript in
preparation.
"The difference between a drunk and an alcoholic
is that a drunk doesn't have to attend all those meetings."

Arthur Lewis

Therefore:

working with alcohols results in strange side-effects.

Alle mie nonne.

Table of Contents

Introduction

1 Overview 3

1.1 The Fluorous Catalyst 5
1.2 Special fluorous techniques 8
1.3 Oxidations in FBS 10

2 Objectives 14

Results and Discussion

1 Cu-catalyzed Alcohol Oxidation 19

1.1 Alcohol Oxidation in FBS 21
1.1.1 Ligand Synthesis 22
1.2 Reactivity improvement for aliphatic secondary alcohols 24
1.2.1 Solvents and temperature 25
1.2.2 Metal and counterion 25
1.2.3 The co-catalyst TEMPO 28
1.3 Compatibility with functional groups 32
1.4 Selectivities in cyclohexanols oxidation 36
1.5 Fluorous tertiary amines and their use as ligands 40
1.6 Summary 44

2 Oxidative Coupling in FBS 45

2.1 Aerobic phenol homocoupling in FBS 47
2.2 Aerobic C-N coupling with arylboronic acids in FBS 49
2.3 Synthesis of fluorous imidazoles as ligands for C-N oxidative coupling 51
2.4 Summary 57
I
3 Ruthenium catalyzed aerobic epoxidation in FBS 58

3.1 Synthesis of the catalyst 60
3.2 FBS epoxidations with Ru(III)-Rf Bimpy 63
2
3.3 FBS alcohol oxidation with Ru(III)-Rf Bimpy 67
2
3.4 Summary 68

4 Fluorous oxazolines 69

5 Summary and Overlook 72

Experimental section

1 General conditions 77

2 Typical Procedures 80

2.1 Typical procedures for oxidations in Fluorous Biphase System 80
TP 1 Typical procedure of alcohol oxidation in FBS 80
TP 2 Typical procedure of alkene epoxidation in FBS 81

2.2 Typical procedures for preparation of starting materials 82
TP 3 Synthesis of benzotriazole diamine derivatives 82
TP 4 Synthesis of fluorous tertiary amines 82
TP 5 Reduction of ketones to cis/trans cyclohexanols 83

3 Synthesis of fluorous Organometallic Reagents 84

4 Cu(II)-catalyzed Aerobic Oxidation of Alcohols in FBS 86

4.1 Synthesis of fluorous ponytails 86
4.2 Synthesis of fluorous TEMPO und pyridines 91
4.3 Alcohol oxidation 94
II