Regioselective synthesis of functionalized salicylates, isotetronic acids, and alkylidene isobenzofurans based on one-pot cyclizations of silyl enol ethers [Elektronische Ressource] / vorgelegt von Rüdiger Dede

Regioselective Synthesis of Functionalized Salicylates, Isotetronic
Acids, and Alkylidene-Isobenzofurans based on One-Pot
Cyclizations of Silyl Enol Ethers




Dissertation

zur
Erlangung des Doktorgrades
doctor rerum naturalium (Dr. rer. nat.)
der Mathematisch-Naturwissenschaftlichen Fakultät
der Universität Rostock







vorgelegt von
Rüdiger Dede, geb. am 3. Juni 1977 in Stade
aus Rostock

Rostock, April 2008


[URN: urn:nbn:de:gbv:28-diss2008-0067-5]
Die Deutsche Nationalbibliothek übernimmt diese Publikation in ihre Sammlung
von Online-Dissertationen.

Dede, Rüdiger:
Regioselective Synthesis of Functionalized Salicylates, Isotetronic Acids, and
Alkylidene-Isobenzofurans based on One-Pot Cyclizations of Silyl Enol Ethers

URN: urn:nbn:de:gbv:28-diss2008-0067-5





Dekan: Prof. Dr. Dieter Neßelmann



Gutachter:
1. Prof. Dr. Peter Langer, Universität Rostock
2. Prof. Dr. Jens Christoffers, Universität Oldenburg



Tag der mündlichen Prüfung: 10. Juni 2008
1. Prüfer: Prof. Dr. Peter Langer (Hauptfach: Organische Chemie)
2. Prüfer: PD Dr. Birgit Tiefenbach (Nebenfach: Toxikologie)


Tag des öffentlichen Kolloquiums: 15. Juli 2008
Die vorliegende Arbeit wurde in der Zeit vom Oktober 2003 bis September 2005 am Institut
für Chemie und Biochemie der Ernst-Moritz-Arndt-Universität Greifswald und vom Oktober
2005 bis April 2008 am Institut für Chemie der Universität Rostock angefertigt.









Who of you by worrying can add a single hour to his life?


Matthew 6:27








Es gibt keinen Menschen auf der Welt, von dem man nicht etwas
lernen könnte.


Albert Schweitzer



Table of Contents

1 Introduction .................................................................................................................. 1
2 Synthesis of Mono-Silyl Enol Ethers and 1,3-Bis-Silyl Enol Ethers ........................ 2
3 Reactions of γ-Azido- β-hydroxyketones..................................................................... 4
3.1 Introduction............................................................................................................... 4
3.2 Synthesis of Starting Materials................................................................................. 5
3.2.1 1-Tosylpropan-2-one ...................................................................... 5
3.2.2 Synthesis of Azidoketones .................................................................................. 5
3.2.3 Synthesis of γ- and δ-Azido- β-hydroxyketones.................................................. 5
3.3 Reactions with PPh .................................................................................................. 9 3
3.4 Conclusion..............................................................................................................11
4 Synthesis of Functionalized Acetophenones and Cyanobenzoates by [3+3]
Cyclizations ................................................................................................................. 12
4.1 Introduction.............................................................................................................12
4.2 Synthesis of Starting Materials............................................................................... 12
4.2.1 Substituted Acetylacetones13
4.2.1.1 3-Formylacetylacetone................................................................................
4.2.1.2 Triacetylmethane.........................................................................................14
4.2.1.3 3-Cyanoacetylacetone..................................................................................
4.2.2 Silylation of Substituted Acetylacetones .......................................................... 15
4.3 [3+3] Cyclizations..................................................................................................16
4.3.1 Synthesis of Functionalized Acetophenones.....................................................
4.3.1.1 Products and Reaction Pathway .................................................................. 16
4.3.1.2 Proof of Structure ........................................................................................ 19
4.3.2 Synthesis of Cyanobenzoates............................................................................ 22
4.4 Conclusion..............................................................................................................23
5 Synthesis of 4-Alkoxycarbonyl-butenolides ............................................................. 24
5.1 Introduction.............................................................................................................24
5.2 Synthesis of Starting Materials............................................................................... 25
5.3 Cyclizations with Oxalyl Chloride ......................................................................... 26
5.3.1 Products26
5.3.2 Mechanism........................................................................................................28
5.3.3 Further Experiments..........................................................................................28
5.4 Synthesis of an Enantiomerically Pure Isotetronic Acid ........................................ 31
5.5 Functionalization by Suzuki Coupling ................................................................... 33
5.6 Conclusion..............................................................................................................34
6 Synthesis of Alkylidene-Isobenzofurans 35
6.1 Introduction.............................................................................................................35
6.2 Synthesis of Starting Materials............................................................................... 36
6.3 Reactions of Silyl Enol Ethers with Phthaloyl Chloride......................................... 36
6.3.1 Products and Reaction Pathway........................................................................ 36
6.3.2 Proof of Structures ............................................................................................ 42
6.4 Conclusion..............................................................................................................44
7 Summary ..................................................................................................................... 45
I
8 Experimental Section ................................................................................................. 46
8.1 Material and Methods ............................................................................................. 46
8.1.1 General Remarks...............................................................................................46
8.1.2 Methods for Compound Characterization and Analysis ...................................
8.1.3 Chromatographic Methods................................................................................48
8.2 General Procedures (GP)........................................................................................49
8.3 Explicit and Compound Characterization............................................ 51
8.3.1 Azido- β-hydroxyketones and Precursors .......................................................... 51
8.3.2 Pyrroles.............................................................................................................57
8.3.3 Rearrangement..................................................................................................58
8.3.4 Starting Materials for [3+3] Cyclizations ......................................................... 59
8.3.5 [3+3] Cyclizations62
8.3.5.1 Functionalized Acetophenones....................................................................
8.3.5.2 Cyanobenzoates...........................................................................................70
8.3.6 4-Alkoxycarbonyl-butenolides and Precursors.................................................73
8.3.6.1 3-Hydroxycarbonyl Compounds.................................................................
8.3.6.2 Bis-Silyl Enol Ethers Derived from 3-Hydroxycarbonyl Compounds........ 83
8.3.6.3 Isotetronic Acids..........................................................................................90
8.3.6.4 Triflates Prepared from Isotetronic Acids ................................................... 97
8.3.6.5 Suzuki Coupling Products ........................................................................... 99
8.3.7 Alkylidene-Isobenzofurans.............................................................................105
9 References ................................................................................................................. 113
10 Appendix ................................................................................................................... 122
10.1 Crystallographic Data...................................................