Table Of ContentNew 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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Description:deficient alkenes were reported by Allgäuer and Mayr.46 Cycloadduct .. aminonitrile 82139 was reacted with the Zincke salt 81 (Scheme 37).147.
