CATALYTIC OXIDATIVE CARBONYLATION OF AMINO ALCOHOLS AND DIAMINES

96 Pages·2007·1.03 MB·English

CATALYTIC OXIDATIVE CARBONYLATION OF AMINO ALCOHOLS AND DIAMINES
TO UREAS AS AN ALTERNATIVE TO PHOSGENE DERIVATIVES: SYNTHESIS OF
DISUBSTITUTED HYDANTOINS

By

DELMY DIAZ-MONTERROSO

A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL
OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT
OF THE REQUIREMENTS FOR THE DEGREE OF
DOCTOR OF PHILOSOPHY

UNIVERSITY OF FLORIDA

2007
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© 2007 Delmy Díaz-M.

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To my daughters Paola and Anabella; and to my husband, Alvaro, for their unconditional love
and support.

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ACKNOWLEDGMENTS
First I would like to thank my daughters Paola and Anabella, who have been there for me
always with their constant love and support along the duration of my studies. They suffered the
most from my long hours at the lab, my frustrations, and my absences without complaint. On the
contrary, they were always understanding and waiting for me patiently. Special thanks go to my
husband Alvaro, for his unconditional love, support, and enthusiasm, and for always believing in
me. I thank my family in Honduras for their never-ending support and encouragement
throughout all these long years of studying away.
I also want to express my gratitude to my advisor, Professor Lisa McElwee-White, for her
guidance and valuable comments and suggestions throughout this academic program and
experimental investigation. I can not thank her enough for all her assistance and for always being
willing to listen to new ideas and encouraging me to try things I never thought were possible. I
also want to thank the members of my committee, Dr. Castellano, Dr. Dolbier, Dr. Lyons and Dr.
Percival, for their helpful suggestions and wise advice.
Special thanks must go to the members of the group for making my life easier and
providing a nice environment to work in. I thank my good friends Ece, Laurel and Marie for
always being there, and for sharing with me many coffee breaks. I also need to thank Phil, Seth,
and Ampofo, with whom I was working every day for the last three years.
Acknowledgement is made to the Pedagogic University Francisco Morazán for their
financial support.

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TABLE OF CONTENTS

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ACKNOWLEDGMENTS ...............................................................................................................4
LIST OF TABLES ...........................................................................................................................7
LIST OF FIGURES .........................................................................................................................8
LIST OF ABBREVIATIONS ..........................................................................................................9
ABSTRACT ...................................................................................................................................11
CHAPTER
1 INTRODUCTION AND LITERATURE REVIEW ..............................................................12
Literature Review ...................................................................................................................13
Transition Metal-Catalyzed Oxidative Carbonylation of Amines to Ureas ....................13
Palladium-catalyzed oxidative carbonylation of amines ..........................................14
Homogeneous carbonylation of amines to ureas ......................................................14
Pd catalysis in ionic liquids ......................................................................................17
Electrocatalytic carbonylation ..................................................................................18
Mechanistic studies ..................................................................................................19
Other Late Transition Metal Catalysts ............................................................................20
Nickel-catalyzed oxidative carbonylation ................................................................20
Ruthenium-catalyzed oxidative carbonylation .........................................................21
Cobalt- and Rhodium-catalyzed oxidative carbonylation ........................................26
Gold-catalyzed oxidative carbonylation ...................................................................29
Tungsten-Catalyzed Oxidative Carbonylation of Amines ..............................................30
Carbonylation of primary amines .............................................................................30
Carbonylation of primary and secondary diamines to cyclic ureas .........................32
Conclusions.............................................................................................................................42
2 SELECTIVE CATALYTIC OXIDATIVE CARBONYLATION OF
AMINOALCOHOLS TO UREAS .........................................................................................44
Results and Discussion ...........................................................................................................45
Carbonylation of 5-Aminopentanol .................................................................................46
Carbonylation of 4-Amino-2-methylbutan-1-ol ..............................................................47
Carbonylation of 1,3-Aminoalcohols ..............................................................................49
Carbonylation of 1,2-Aminoalcohols ..............................................................................52
Conclusions.............................................................................................................................54

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3 THE W(CO) /I CATALYZED OXIDATIVE CARBONYLATION OF DIAMINES:
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ANALOGS OF THE CORE STRUCTURES OF THE HIV PROTEASE INHIBITORS
DMP 323 AND DMP450. ......................................................................................................56
Background .............................................................................................................................56
Results and Discussion ...........................................................................................................61
Synthesis of Seven-Membered Ring Cyclic Ureas 84 and 89 .........................................61
Conclusions.............................................................................................................................64
4 CATALYTIC OXIDATIVE CARBONYLATION OF ENANTIOMERICALLY PURE
-AMINO AMIDES TO PRODUCE HYDANTOIN DERIVATIVES ................................65
Background .............................................................................................................................65
Classic Ways to Synthesize Hydantoins .................................................................................65
Solution Phase Synthesis .................................................................................................67
Solid-Phase Organic Synthesis ........................................................................................69
Synthesis of Hydantoins Using W(CO) /I Catalytic System .........................................70
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Results and Discussion ...........................................................................................................71
Conclusions.............................................................................................................................76
5 EXPERIMENTAL SECTION ................................................................................................77
General Procedures ..........................................................................................................77
Procedure A for Carbonylation of Amino Alcohols with CDI ........................................77
Procedure B for carbonylation of aminoalcohols with DMDTC ....................................77
Procedure C for Catalytic Carbonylation of Amino Alcohols with W(CO) /I ..............78
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Synthesis of Cyclic Ureas .......................................................................................................82
General Procedure for the Synthesis of -Amino Amides 103a-103e. ..................................84
General Procedure for the Carbonylation of -Amino Amides 103a-e to Afford
Hydantoins 104a-e. .............................................................................................................84
LIST OF REFERENCES ...............................................................................................................87
BIOGRAPHICAL SKETCH .........................................................................................................96

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LIST OF TABLES
Table page

1-1. Oxidative Carbonylation of Primary Amines to Ureas under Optimized Conditions. ..........33
1-2. Oxidative Carbonylation of Substituted Primary Diamines ..................................................36
1-3. Catalytic Carbonylation of Substituted Benzylamines to Ureas ..........................................38
1-4. Yields of Bicyclic Ureas from Diamines 46a-49a ................................................................42
2-1. Carbonylation of aminoalcohols to ureas and carbamates. ....................................................48
3-1. Structures of cyclic urea inhibitors ........................................................................................58
3-2. Carbonylation of compounds 35-37 to Ureas 38-40 .............................................................60
4-1. Carbonylation conditions for -amino amide 103a. ..............................................................72
4-2. Synthesis of α-amino amides 103a-d ....................................................................................74
4-3. Catalytic carbonylation of α-amino amides 103a-e to hydantoins 104a-e. ...........................75

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LIST OF FIGURES
Figure page

1-1. Co(salen) (22) and modified Co(salen) complexes (23-27) ..................................................28
1-2. Structures of the HIV protease inhibitors DMP 323 and DMP 450 ......................................39
4-1. Hydantoin ring structure. .......................................................................................................66
4-2. Synthetic strategies and building blocks for hydantoin synthesis. ........................................66
4-3. α-Amino amide substrates to be converted to hydantoins .....................................................73

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LIST OF ABBREVIATIONS
CDI 1,1'-Carbonyldiimidazole
DBU 1,8-diazabicyclo[5.4.0]undec-7-ene
DCB 1,4-dichloro-2-butene
DCE Dichloroethane
DCM Dichloromethane
DEA Diethylamine
DIBAL Diisobutylaluminium hydride
DMA N,N-dimethylacetamide
DMAP 4-dimethyl aminopyridine
DMDTC S,S'-dimethyl dithiocarbonate
DME 1,2-dimethoxyethane
DMF Dimethylformamide
DMImBF 1-decyl-3-methylimidazolium tetrafluoroborate
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DMSO Dimethyl sulfoxide
DPT Di-2-pyridylthiocarbonate
DPU Diphenylurea
EMImBF 1-ethyl-3-methylimidazolium tetrafluoroborate
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GC-MS Gas chromatograph-mass spectrometer
GLC Gas liquid chromatography
HIV Human immunodeficiency virus
MAC Mixed anhydrides coupling
MEM 2-methoxyethoxymethyl
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NMP N-methylpyrrolidinone
SEM 2-(trimethylsilyl)ethoxymethyl
SPOS Solid-phase organic synthesis
THF Tetrahydrofuran
TLC Thin layer chromatography

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