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 Público

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

About this Master's Thesis

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School	Laney Graduate School
Department	Chemistry
Degree	MS
Submission	Master's Thesis
Language	English
Research Field	Chemistry, Organic Chemistry, Inorganic
Palavra-chave	molybdenum organometallic enantiomeric scaffolding
Committee Chair / Thesis Advisor	Liebeskind, Lanny S, Emory University
Committee Members	Liotta, Dennis C, Emory University MacBeth, Cora, Emory University

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