Organometallic Enantiomeric Scaffolds in the Synthesis of Alkaloids: I. Homo-SN2´-like Reaction/Annulative Demetallation and the Application in the Synthesis of (+)-Isofebrifugine II. Uncatalyzed Electrophilic C-C Bond Forming Reactions of Pyranyl and Pyridinyl Molybdenum Complexes Pubblico
Chen, Wenyong (2010)
Abstract
Chapter One A novel homo-SN2'-like reaction between neutral
TpMo(CO)2(5-acyloxy-
η3-pyranyl) and TpMo(CO)2(5-acyloxy-η3-pyridinyl)
scaffolds and a variety of
stabilized carbonanion nucleophiles provided a powerful methodology
to construct C-C
bonds stereoselectively. Moreover, it proceeded through an
interesting anionic
mechanism and preliminary mechanistic study was reported. Based on
the Mo complex
produced in the reaction, a mechanistically related annulative
demetallation was
developed to furnish the framework of 2,7-dioxabicyclo[4.3.0]nonane
and 2-aza-7-
oxabicyclo[4.3.0]nonane in good to excellent yields. In order to
demonstrate the power of
this new reaction sequence, (+)-isofebrifugine was synthesized in a
concise route by
employing the homo-SN2'-like-annulative demetallation
sequence.
Chapter Two Neutral
TpMo(CO)2(5-trifluoroacetate-η3-pyranyl) and
TpMo(CO)2(5-
trifluoroacetate-η3-pyridinyl) scaffolds underwent an
uncatalyzed Friedel-Crafts-like
reaction with a variety of electron-rich arenes and olefins to form
substitution products in
high yields. A preliminary study of the mechanism showed that
TpMo(CO)2(5-
trifluoroacetate-η3-pyranyl) in DMSO rapidly rearranged to
TpMo(CO)2(2-
trifluoroacetate-η3-pyranyl) complex first, which then reacted
with indole derivatives. By
contrast, TpMo(CO)2(5-trifluoroacetate-η3-pyranyl) in
acetonitrile or chloroform reacted
with electron-rich arenes and olefins without the initial
rearrangement. And, silyl enol
ethers and allylsilanes could only react with the unrearranged
TpMo(CO)2(5-
trifluoroacetate-η3-pyranyl) complex. Further annulative
demetallation proved to be
successful with a series of substrates to form oxygen heterocycles
and carbocycles in 5 or
6 membered rings in a mild condition. This methodology has been
successfully utilized to
access the tetracyclic structure of vindoline in a model
system.
Chapter Three A short, practical route to a versatile
5-oxo-4-methyl-(η-2,3,4)-
allylmolybdenum pyranyl and
5-oxo-4-methyl-(η-2,3,4)-allylmolybdenum pyridinyl
scaffold has been developed using the Achmatowicz rearrangement.
Further
transformation through reduction and dehydration enabled a rapid
access to Δ5-4-methyl-
(η-2,3,4)-allylmolybdenum pyridinyl scaffold.
Table of Contents
Contents
Chapter One The Development of Homo-SN2´-like
Reaction/Annulative Demetallation
and the Application in the Synthesis of (+)-Isofebrifugine
................................................ 1
Background.....................................................................................................................
2
Palladium catalyzed allylic substitution
......................................................................
2
Molybdenum catalyzed asymmetric allylic substitution
............................................. 5
Iridium catalyzed asymmetric allylic
substitution.....................................................
10
Introduction
...................................................................................................................
16
Results and Discussion
..................................................................................................
17
Initial studies and project design
...............................................................................
17
Homo-SN2´-like reaction
...........................................................................................
21
Mechanistic consideration
.........................................................................................
31
An important side reation: ring
opening....................................................................
35
Demetallation.............................................................................................................
37
Total synthesis of (+)-isofebrifugine
.........................................................................
44
Conclusion.....................................................................................................................
54
References
.....................................................................................................................
55
Experimental
Section.....................................................................................................
56
Chapter Two Uncatalyzed Electrophilic C-C Bond Forming
Reactions of Pyranyl and
Pyridinyl Molybdenum Complexes. A synthetic Tactic for the
Enantioselective
Construction of Indole
Alkaloids....................................................................................
102
Background..................................................................................................................
103
Stoichiometric transition metal mediated electrophilic
reactions............................ 103
Cobalt
Complex.......................................................................................................
103
Iron
Complex...........................................................................................................
105
Molybdenum
complex.............................................................................................
108
Introduction
.................................................................................................................
111
Results and
discussion.................................................................................................
113
Study in the typical Homo-SN2´-like reaction
condition......................................... 113
Preparation of new substrate and discovery of an uncatalyed
Friedel-Crafts reaction
................................................................................................................................
115
Mechanistic consideration
.......................................................................................
117
Uncatalyed Friedel-Crafts reaction in pyridinyl molybdenum
scaffold.................. 121
Studies on various indole
derivatives..............................................................125
Uncatalyzed Friedel-Crafts reaction with electron-rich olefins
.............................. 130
Demetallation...........................................................................................................
134
Application to the synthesis of natural products
..................................................... 138
Conclusion...................................................................................................................
142
References
...................................................................................................................
143
Experimental
Section...................................................................................................
145
Chapter Three Synthesis of 4-Methyl Substituted Pyranyl and
Pyridinyl Scaffold..... 193
Background..................................................................................................................
194
Introduction
.................................................................................................................
196
Results and
discussion.................................................................................................
197
Synthesis of 4-methoxy scaffold 3.2
.......................................................................
197
The first route to scaffold 3.1
..................................................................................
198
Synthesis of the oxygen scaffold 3.14
.....................................................................
200
Synthesis of the scaffold
3.17..................................................................................
202
Synthesis of the scaffold
3.1....................................................................................
203
Study on the [5+2] reaction of scaffold
3.1.............................................................
206
Conclusion...................................................................................................................
207
References
...................................................................................................................
208
Experimental
Section...................................................................................................
209
About this Dissertation
School | |
---|---|
Department | |
Degree | |
Submission | |
Language |
|
Research Field | |
Parola chiave | |
Committee Chair / Thesis Advisor | |
Committee Members |
Primary PDF
Supplemental Files
Thumbnail | Title | Date Uploaded | Actions |
---|