New Synthetic Strategies towards Indolizines and Pyrroles

277 Pages·2015·7.47 MB·English

New Synthetic Strategies towards
Indolizines and Pyrroles

Dissertation zur Erlangung des Grades
Doktor der Naturwissenschaften

vorgelegt am Fachbereich Chemie, Pharmazie und Geowissenschaften
der Johannes Gutenberg-Universität Mainz

von
Murat Kücükdisli
geboren in Düzce, Türkei

Mainz
2015

Datum der mündlichen Prüfung: 28.04.2015
Dekan:
1. Berichterstatter: Prof. Dr. Till Opatz
2. Berichterstatter:

To my family

ACKNOWLEDGEMENTS

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Table of Contents
ACKNOWLEDGEMENTS ............................................................................................... V
LIST OF ABBREVIATIONS ........................................................................................... IX
1 INTRODUCTION ....................................................................................................... 1
1.1 Nitrogen Containing Heteroaromatic Compounds .................................. 1
1.2 Indolizines .................................................................................................... 2
1.2.1 Synthesis of Indolizines ............................................................................. 4
1.2.1.1 Annulation of Pyridines .................................................................. 4
1.2.1.2 Annulation of Pyrroles .................................................................. 10
1.3 Pyrroles ....................................................................................................... 14
1.3.1 Synthesis of Pyrroles ............................................................................... 15
2 MOTIVATION .......................................................................................................... 23
3 RESULTS AND DISCUSSION ................................................................................ 27
3.1 Indolizines .................................................................................................. 27
3.1.1 Decoration of the Pyrrole Unit ................................................................ 27
3.1.1.1 Initial Findings .............................................................................. 27
3.1.1.2 Reaction Optimization .................................................................. 31
3.1.1.3 Substrate Scope ............................................................................. 33
3.1.1.4 Mechanisms and Limitations ........................................................ 36
3.1.2 2-Aminoindolizines ................................................................................. 38
3.1.2.1 Initial Findings .............................................................................. 38
3.1.2.2 Reaction Optimization .................................................................. 42
3.1.2.3 Substrate Scope Studies ................................................................ 43
3.1.2.4 Limitations .................................................................................... 47
3.1.3 Decoration of the Pyridine Unit............................................................... 48
3.1.3.1 Initial Findings .............................................................................. 51
3.1.3.2 Reaction Optimization .................................................................. 52
3.1.3.3 Substrate Scope Studies ................................................................ 55
3.2 Pyrroles ....................................................................................................... 60
3.2.1 Pyrrole-2-carbonitriles ............................................................................. 61
3.2.2 2,4-Disubstituted Pyrroles ....................................................................... 63
3.2.3 2,3,5-Trisubstituted Pyrroles ................................................................... 67
3.2.4 Pyrrole-2-carboxamides........................................................................... 70
3.2.5 2,2’-Bipyrroles ......................................................................................... 72
4 CONCLUSION AND OUTLOOK ........................................................................... 75
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CONTENT
5 EXPERIMENTAL SECTION ................................................................................. 81
5.1 General Experimental Methods ............................................................... 81
5.2 Annulation of pyridines ............................................................................ 82
5.2.1 Synthesis of Indolizines from Pyridinium Ylides ................................... 82
5.2.2 Synthesis of 2-Aminoindolizines .......................................................... 115
5.3 Annulation of Pyrroles ............................................................................ 135
5.3.1 Synthesis of Indolizines from Pyrroles ................................................. 135
5.4 Synthesis of Pyrroles ............................................................................... 154
5.4.1 Synthesis of Pyrrole-2-carbonitriles ...................................................... 154
5.4.2 Synthesis of 2,4-Disubstituted Pyrroles ................................................ 160
5.4.3 Synthesis of 2,3,5-Trisubstituted Pyrroles ............................................ 166
5.4.4 Synthesis of Pyrrole-2-carboxamides.................................................... 171
5.4.5 Synthesis of 2,2’-Bipyrroles .................................................................. 177
6 REFERENCES ........................................................................................................ 179
APPENDIX A: NMR SPECTRA ................................................................................... 193
APPENDIX B: X-RAY DATA ....................................................................................... 248
ERKLÄRUNG ................................................................................................................. 265

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