Description: foster77.jpg

 

Foster, C. (1999) Studies Directed Towards the Synthesis of ()-Ebelactone-A, PhD Thesis, Cambridge University

Description: ebelactone.jpg

A paper copy of the thesis is held at the University Library, Cambridge, UK.

Acknowledgements, Abstract and Abbreviations

Chapter 1: Introduction
1.1 The Target Molecule
1
         1.1.1 Introduction
1
1.2 -Lactones
3
         1.2.1 Introduction
3
         1.2.2 Reactions of -Lactones
4
                    1.2.2.1 Decarboxylation
4
                    1.2.2.2 Rearrangement
5
                    1.2.2.3 Nucleophilic Attack
6
                    1.2.2.4 Enolate Formation and Reaction
7
                    1.2.2.5 Conclusion
10
        1.2.3 Synthesis of -Lactones
10
                    1.2.3.1 Cyclisation of -Halocarboxylic Acid Salts
10
                    1.2.3.2 Cyclisation of -Hydroxycarboxylic Acids
11
                    1.2.3.3 [2+2] Cycloaddition Reactions
13
                    1.2.3.4 Other Methods
15
1.3 Paterson Synthesis of Ebelactone-a
17
1.4 General Organosilicon Chemistry
20
         1.4.1 Introduction and The Nature of the C-Si Bond
20
         1.4.2 Electrophilic Attack Directed by Silicon
22
                    1.4.2.1 Introduction
22
                    1.4.2.2 Alkylation of -Silyl Enolates
23
                    1.4.2.3 Hydroboration of Allylsilanes
23
                    1.4.2.4 SE2' Reaction of Allyl- and Allenylsilanes
25
         1.4.3 The Dimethyl(phenyl)silyl Group as a Masked Hydroxyl
26

Chapter 2: Previous Work
2.1 Retrosynthetic Analysis
28
2.2 Synthesis of the Fragments
28
         2.2.1 Fragment A
30
         2.2.2 Fragment B
41
         2.2.3 Fragment C
44
2.3 Joining the Fragments Together and Completing the Synthesis
55
         2.3.1 Coupling of Fragments B and C
55
         2.3.2 Coupling of Fragment A to the Product of Coupling of Fragments B and C
61
         2.3.3 Final Transformations
64

Chapter 3: Model Coupling Work
3.1 Model Coupling of Fragment A to Fragment BC
65
         3.1.1 Introduction
65
         3.1.2 Vinylmetal-Aldehyde Couplings
65
         3.1.3 The Nozaki-Kishi Reaction
68
         3.1.4 Nozaki-Kishi Model Reactions
70
3.2 Reduction of the Allylic Alcohol
80
         3.2.1 Introduction
80
         3.2.2 Silicon Methods
80
         3.2.3 Carbamate Methodology
82
         3.2.4 Other Reduction Methods
85
3.3 Conclusion
87

Chapter 4: Fragment A and the Model Coupling Reaction
4.1 Introduction
89
4.2 The Aldol Reaction
90
         4.2.1 Introduction
90
         4.2.2 Achiral Enolates with Achiral Aldehydes
91
         4.2.3 Achiral Enolates with Chiral Aldehydes
93
         4.2.4 Chiral Enolates with Chiral Aldehydes
93
4.3 Oppolzer's Sultams as Chiral Auxiliaries
94
         4.3.1 Introduction
94
         4.3.2 Syn and Anti Methodology
95
         4.3.3 The SN' Reaction
98
4.4 Synthesis of Aldehyde 155
99
4.5 The Aldol Reaction
105
4.6 Final Steps
112

Chapter 5: A New Route to Fragment A
5.1 Introduction
115
5.2 Silylcupration of Allenes
117
5.3 Nucleophilic Addition to N--(Silyl)enoylsultams
121
5.4 Model Reactions on Crotonylsultam 218
123
         5.4.1 Allene Methodology
123
         5.4.2 Alternative Route to the Vinylcuprate 199
127
5.5 Synthesis of N--(Silyl)enoylsultam 212
131
5.6 Reaction of Vinylcuprate 199 with Sultam 212
134
5.7 Another Synthesis of Fragment A
137

Chapter 6: Experimental
6.1 Introduction
142
6.2 Compounds for Chapter 3
143
6.3 Compounds for Chapter 4
159
6.4 Compounds for Chapter 5
183

References and Notes

Colin Foster, Cambridge University 1999.

 

Paper

Sarah C. Archibald, David J. Barden, Jrme F. Y. Bazin, Ian Fleming, Colin F. Foster, Ajay K. Mandal, Amit K. Mandal, David Parker, Ken Takaki, Anne C. Ware, Anne R. B. Williams and Anna B. Zwicky (2004) Stereocontrol in Organic Synthesis Using Silicon-Containing Compounds: Studies Directed Towards the Synthesis of Ebelactone-A, Org. Biomol. Chem., 2, 1051-1064

Colin Foster 2012