I. A New Approach to the Synthesis of a Key 5-Oxo-Pyridinyl Molybdenum Scaffold. II. Oxidative Demetalation of η3-Allylmolybdenum Complexes with an Oxygen Nucleophile; Application to the Synthesis of (+)-Isofebrifugine Analogs Open Access
Goschy, Gregory Nicholas (2010)
Abstract
I. A New Approach to the Synthesis of a Key 5-Oxo-Pyridinyl
Molybdenum Scaffold.
II. Oxidative Demetalation of η3-Allylmolybdenum
Complexes with an Oxygen
Nucleophile; Application to the Synthesis of (+)-Isofebrifugine
Analogs
By Gregory Nicholas Goschy
Due to their versatility, molybdenum π-complexes have become
common
organometallic enantiomeric scaffolds for the construction of a
variety of enantiopure
heterocycles. A concise, high throughput method was developed to
access both racemic
and chiral, non-racemic
TpMo(CO)2(η3-pyridinyl) complexes in an
efficient manner. In
recent years, the use of a key 5-oxo-pyridinyl scaffold has become
a major focus for the
Liebeskind laboratory. Although there have been many improvements
to the preparation
of this key scaffold, recent increases in the chiral auxiliary
precursor price has hindered
widespread use of this chemistry. Further exploration and screening
of the "chiral pool"
has led to the construction of a variety of inexpensive chiral
auxiliaries, as well as a
different method to incorporate them.
Oxidative demetatalation of η3-allylmolybdenum
complexes is a key step in the
synthesis of numerous biologically active compounds. Expanding the
scope of this
reaction by incorporating oxygen as the nucleophile will provide a
better route towards
the synthesis of (+)-isofebrifugine and its analogs.
Table of Contents
Table of Contents
Chapter One: An Introduction to Organometallic Enantiomeric
Scaffolding
Introduction…………………………………………………………………………………………………………………2
Concept: Transition Metal Complexes in Organic
Synthesis………………………………………3
Preparation of η3-Allyl Molybdenum
π-Complexes………………………………………………………4
The Trispyrazolylborate (Tp)
Ligand……………………………………………………………………………5
Utilization of TpMo(CO)2 Complexes in Organic
Synthesis…………………………………………6
Preparation of a Key 5-Oxo-Pyridinyl Molybdenum
Scaffold………………………………………7
The Aza-Achmatowicz Approach to a Key 5-Oxo-Pyridinyl Molybdenum
Scaffold……10
Exploration of the "Chiral Pool" for Asymmetric
N-Protection……………………...…………12
Synthesis of Enantiopure Substituted Alkaloids from a Key
5-Oxo-Pyridinyl
Molybdenum
Scaffold…………………………………………………………………………………………………13
Chapter Two: Racemization-Free Removal of the Methyl Mandelate
Chiral
Auxiliary
Introduction…………………………………………………………………………………………………………………15
Results and
Discussion………………………………………………………………………………………………16
Optimization of
Hydrogenolysis…………………………………………………………………………………16
Control Experiments and Mechanistic
Insight……………………………………………………………19
Possible Pathways to
Racemization……………………………………………………………………………22
Other Methods for Removal of the Chiral
Auxiliary……………………………………………………23
Conclusion……………………………………………………………………………………………………………………24
Chapter Three: A New Approach to a Key 5-Oxo-Pyridinyl
Organometallic
Enantiomeric Scaffold via Novel Sulfenamide Chiral
Auxiliaries
Introduction…………………………………………………………………………………………………………………26
Background…………………………………………………………………………………………………………………26
Results and
Discussion…………………………………………………………………………………………………27
General Preparation of
Sulfenamides…………………………………………………………………………27
Preparation of Sulfenamide Complexes from Inexpensive Chiral,
Non-Racemic
Alcohols…………………………………………………………………………………………………………………………29
Preparation of Sulfenamide Complexes from Inexpensive Chiral,
Non-
Racemic
Terpenes…………………………………………………………………………………………………………30
Conclusion………………………………………………………………………………………………………………………33
Chapter Four: Oxidative Demetalation of η
3-Allylmolybdenum Complexes with an
Oxygen Nucleophile; Application to the Synthesis of
(+)-Isofebrifugine Analogs
Introduction……………………………………………………………………………………………………………………35
Results and
Discussion……………………………………………………………………………………………………39
Conclusion………………………………………………………………………………………………………………………41
Experimental
Section…………………………………………………………………………………………………42
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