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Modern Amination Methods

Edited by Alfred0 Ricci

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@WILEY-VCH Weinheim Chichester . New York . Toronto . Brisbane . Singapore

Prof. Dr. A. Ricci Dept. of Organic Chemistry University of Bologna Via Risorgimento 4 40136 Bologna Italy

This b k was carefully produced. Nevertheless, authors, editor and publisher do not warrant the information contained therein to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

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Preface

The origin of this book can be traced back at least in part to the fact that the importance and practicality of amination reactions as a tool for obtaining target compounds is nowadays fully acknowledged by chemists in synthetic organic, medicinal, agricultural and natural product chemistry, as well as by the pharmaceutical and agricultural industries. This prominence is due to the explosive development during the past decade of novel and more efficient amination methods. These provide a great improvement with respect to the classical methods such as those based on the attack of a nucleophilic nitrogen atom to an electrophilic carbon, which are hampered by the difficult access to the electrophilic precursors - particularly when multifunctional derivatives are taken into consideration - and by the frequently recurring difficult reaction conditions.

This book is intended to provide an overview of several areas of research in which amination plays a key role, and to introduce the reader to new concepts that have been developed quite recently for generating new C - N bonds. As the pharmaceutical and chemical industries move rapidly away from the development of racemic compounds, the access to synthetic routes that lead efficiently to enantiomerically pure materials is becoming increasingly important. For this reason, most of the contributions in this book refer to asymmetric synthesis. However, no attempt has been made to present a comprehensive work, and important areas such as asymmetric hydroxyamination [ 11 have not been dealt with. Furthermore, it may be worth men- tioning that viable, useful and comprehensive sources of information about the meth- odological approaches to electrophilic amination developed since 1985 have already been reported [2], and that a chapter in Houben-Weyl reviewing several aspects of the asymmetric electrophilic amination [3] compiles important contributions up to 1995.

In order to provide - whenever possible - new perspectives in the different areas treated in the book, the authors have been recruited among internationally recog- nized experts in their specific fields.

This book is arranged in seven chapters which cover the following aspects of amination - even if the order of the contributions is somewhat arbitrary. Chapter 1 (K. A. Jdrgensen) deals with modem aspects of allylic amination reactions for pre- paring fundamental building blocks which have either distinct important properties or can be used for further transformations in organic synthesis. Two approaches - the

VI Preface

nucleophilic allylic substitution and the direct allylic amination of simple alkenes - are described. Considering the potential importance of electrophilic amination of alkenes, progress and steps being taken to carry out indirect amination of organometallics derived from hydroboration and hydrozirconation of alkenes are also described in Chapter 2 (E. Fernandez and J.H. Brown). In Chapter 3, J.-P. Genet, C. Greck and D. Lavergne provide an exhaustive overview of modem methods (up to 1998) based on the stereoselective electrophilic amination of chiral carbon nucleophiles for making a- and p-amino acid derivatives. Chapter 4 (H. Kunz, H. Tietgen and M. Schultz-Kukula) also addresses the synthesis of a- and p-amino acids with high enantiomeric purity, but a different approach based on the reaction of carbohy- drate-derived prochiral imines with nucleophiles is used. More about the use of organometallics is to be found in the following two chapters. Thus, Chapter 5 (E. Carreira, C.S. Tomooka and H. Iikura) focuses on the various methods that have been reported for the synthesis of metal nitride complexes. These complexes have an intriguing array of reactivity and structure, and display a host of desirable properties in material sciences, medicine and chemical synthesis. The nitrogen atom transfer from a nitrido complex is reviewed in Chapter 6 by M. Komatsu and S. Minakata, with special emphasis on enantioselective transformations in aziridination reactions using nitridomanganese complexes. A fairly new approach to C - N bond formation - the transition metal-catalyzed synthesis of arylamines - is the aim of Chapter 7, in which J. F. Hartwig provides an exhaustive account of the palladium- catalyzed amination of aryl halides and sulfonates for use in complex synthetic problems. The breakthrough required to convey efficiency and high performance is the catalyst design, and many new challenges remain for the synthetic chemist in this area.

Complete reference citations have been provided since, as it is increasingly re- cognized, they are a requirement for manuscripts and proposals.

It is my sincere hope that this book will provide synthetic chemists with new opportunities for achieving their synthetic goals. For those students who are reading the book in order to enhance their synthetic “toolkit”, I hope they will enjoy the variety of these new reactions which span from stoichiometric to catalytic, from natural product-based protocols to synthetic strategies employing organometallic complexes.

I gratefully acknowledge the work done by all authors in presenting up-to-date and well-referenced contributions. Without their effort this volume would not have been possible. Furthermore, it was a pleasure to contribute with the Wiley-VCH “crew” in Weinheim, who not only did an excellent job in producing the book, but also helped me in a competent manner in all phases of its preparation. Finally, I am grateful to Dr. Golitz and to Dr. Eckerle who originally encouraged the idea of creating a book about Modern Amination Methods.

Bologna, January 2000 Alfred0 Ricci

Preface VII

References

[ I ] (a) G. Li, H.-T. Chang, K. B. Sharpless, Angew. Chem. Int. Ed. Engl. 1996.35.451; (b) G. Li, H. H. Angert, K. B. Sharpless, Angew. Chem. Int. Ed. Engl. 1996,352813; (c) H. C. Kolb, K. B. Sharp- less, Asymmetric Aminohydroxylation in Transition Metals for Organic Synthesis, Vol. 2; M. Beller, C. Bolm (Eds.); WILEY-VCH, Weinheim, 1998,243 - 260; (d) G. Schlingloff, K. B. Sharp- less, Asymmetric Aminohydroxylation in Asymmetric Oxidation Reactions: A Practical Approach; T. Katsuki (Ed.); Oxford University Press, Oxford, in press. E. Erdik, M. Ay, Chem. Rev. 1989, 89, 1947. G. Boche in Houben-Weyl. Methods of Organic Chemistry, Stereoselective Synthesis, Vol. E21e; G. Helmchen, R. W. Hoffmann, J. Mulzer, E. Schaumann (Eds.); Thieme, Stuttgart, 1995, 5133 - 5156.

[2] [3]

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Contents

Preface V List of Authors XV

Chapter 1 Modem Allylic Amination Methods 1 Karl Anker J@rgensen

1.1 1.2 1.2.1 1.2.2 1.2.2.1

1.2.3

1.2.4 1.2.5 1.2.5.1

1.2.5.2 1.2.6 1.3

Introduction 1 Nucleophilic Amination of Functionalized Alkenes Amination of Allyl Alcohols 3 Amination of Allyl halides 6 Amination of Allyl Halides and Acetates Catalyzed by metal Complexes 8 Electrophilic Amination of Non-Functionalized Alkenes 14 Amination with Nitrene Complexes 15 Amination Based on Ene-Like Processes Type 1 Reactions: Ene Reaction Followed by [2,3]-Sigmatropic Rearrangement 19 Type 2 Ene Reactions 22 Allylic Amination with Ar-NX and a Metal Catalyst Summary 32

2

16

27

Acknowledgments 33 References 33

Chapter 2 Eletrophilic Amination Routes from Alkenes 37 Elena Fernandez and John M . Brown

2.1 Introduction 37 2.2 Indirect Stoichiometric Amination 37 2.2.1 Amination via Organoboron Compounds 38 2.2.1.1 Applications to the Synthesis of Primary Amines 41 2.2.1.2 Applications to the Synthesis of Secondary Amines 46 2.2.1.3 Applications to the Synthesis of Tertiary Amines 5 1 2.2.2 Amination via Organozirconium Compounds 5 1

X Contents

2.3 Indirect Catalytic Amination 52 2.4 Direct Alkene Amination 59 References 6 1

Chapter 3 Stereoselective Electrophilic Amination with Sulfonyloxycarbamates and Azodicarboxylates 65 Jean-Pierre Genet, Christine Greck and Damien Lavergne

3.1 3.2 3.2.1 3.2.2

3.2.2.1 3.2.2.2 3.2.3

3.3 3.3.1 3.3.2 3.3.3 3.3.3.1 3.3.3.2 3.3.4 3.3.5

3.3.5.1 3.3.5.2 3.4 3.4.1 3.4.2 3.5

Introduction 65 Sulfonyloxycarbamates 67 Preparation of N-[(arylsulfonyl)oxy]carbamates 67 Stereoselective Synthesis of a-Amino Carboxylic and Phosphonic Acids via Electrophilic Amination with Lithium rerr-Butyl N-(tosyloxy) Carbamate 68 a-Amino Carboxylic Acids 68 a-Amino Phosphonic Acids 68 Reactions of Ethyl N-((p-nitrobenzenesulfonyl)oxy(carbamate with Chiral Enamines and Enol Ethers 69 Dialkylazodicarboxylates 7 1 Electrophilic Amination of Silyl Ketene Acetals 72 Electrophilic Amination of Chiral Amide Enolates 76 Electrophilic Amination of Chiral Ester Enolates 80 j3-Hydroxy Esters 80 P-Amino Esters 86 Electrophilic Amination of Ketone Enolates Electrophilic Amination of Phosphorous Stabilized Anions 91 Oxazaphospholanes 92 Diazaphospholidines 94 Chiral Electrophilic Aminating Reagents 96 Azodicarboxylates and Azodicarboxamides 96 Chiral Catalytic Approach 99 Conclusion 10 1

88

References 10 1

Chapter 4 Glycosylamines as Auxiliaries in Stereoselective Syntheses of Chiral Amino Compounds 103 Heiko Tietgen, Martin Schultz-Kukula and Host Kunz

4.1 Introduction 103 4.1.1 Exo Anomeric Effect 104 4.1.2 Influence of Coordinating Centers 105 4.1.3 Pseudo-Enantiomeric Carbohydrates in Stereoselective

Syntheses 105

Contents XI

4.2 Syntheses of Amino Acids 106 4.2.1 Syntheses of Enantiomerically Pure a-Amino Acids 106 4.2.2 Syntheses of Enantiomerically Pure P-Amino Acids 108 4.2.3 Rearrangement Reactions 111 4.2.4 Stereoselective Multicomponent Reactions 1 14 4.3 Stereoselective Syntheses of Chiral Heterocycles 1 18 4.3.1 Heterocycles Through Cycloaddition Reactions 118 4.3.2

4.4 Conclusion 127 References 127

Stereoselective Syntheses of Chiral Piperidines via Addition Reactions to 4-Pyridones 125

Chapter 5 Syntheses of Transition Metal Nitride Complexes 129 Craig S. Tomooka, Hitoshi likura and Erick M. Carreira

5.1 5.2

5.2.1 5.2.2 5.2.3 5.2.4 5.2.5 5.3 5.4 5.4.1 5.4.2 5.4.3 5.4.4 5.4.5 5.4.6 5.4.7 5.4.8 5.4.9 5.4.10 5.5

Introduction 129 Nitrogen-Atom Sources for the Reparation of Metal Nitrides 130 N3- Reagents 13 1 N2- Reagents 132 N1- Reagents 132

Reagents 133 Other Reagents 134 Ligands in Metal Nitride complexes 134 Transition Metal Nitride Complexes 140 Vanadium 140 Tantalum 142 Chromium 143 Molybdenum 146 Tungsten 150 Manganese 152 Technicium 155 Rhenium 157 Ruthenium 159 Osmium 161 Conclusion 164

References 165

Chapter 6 Asymmetric Nitrogen Transfer with Nitridomanganese Complexes 169 Satoshi Minakuta and Mitsuo Komutsu

6.1 Introduction 169 6.2 Achiral Nitrogen Atom Transfer to Olefins 170

XI1 Contents

6.2.1

6.2.2

6.3 6.4

6.4.1

6.4.2

6.4.3 6.4.4 6.4.5 6.5

Nitrogen Atom Transfer Reaction with Achiral Nitrido Complexes 170 Nitrogen Atom Transfer Aziridination of Olefins with Other Nitrogen Sources 174 Synthesis of Chiral Nitridomanganese Complex 177 Asymmetric Aziridination of Olefins with Chiral Nitridomanganese Complexes 179 Asymmetric Aziridination of Styrene with Nitrido Complex 179 The Asymmetric Aziridination of Styrene with a Variety of Nitrido Complexes Asymmetric Aziridination of Styrene Derivatives Aziridination of Conjugated Dienes 188 Asymmetric Amination of Silyl Enol Ether 191 Conclusion 192

183 185

References 193

Chapter 7 Palladium-Catalyzed Amination of Aryl Halides and Sulfonates 195 John E Hartwig

7.1 7.1.1 7.1.2

7.1.3 7.1.4 7.2 7.2.1 7.2.2 7.3

7.3.1

7.3.1.1 7.3.2 7.3.2.1 7.3.2.2 7.3.2.3 7.3.2.4 7.3.2.5 7.3.3

Introduction 195 Synthetic Considerations 195 Prior C-X Bond-Forming Coupling Related to the Amination of Aryl Halides 197 Novel Organometallic Chemistry 197 Organization of the Chapter 198 Background 199 Early Palladium-Catalyzed Amination 199 Initial Synthetic Problems to be Solved 201 Palladium-Catalyzed Amination of Aryl Halides Using Amine Substrates 201 Initial Intermolecular Tin-Free Aminations of Aryl Halides 201 Initial Intramolecular Amination of Aryl Halides 203 Second-Generation Catalysts: Aryl Bisphosphines 204 Amination of Aryl Halides 204 Amination of Aryl Triflates 208 Amination of Heteroaromatic Halides 209 Amination of Solid-Supported Aryl Halides 211 Amination of Polyhalogenated Aromatic Substrates 2 11 Third-Generation Catalysts with Alkylmonophosphines: High Turnover Numbers, General Amination of Bromides at Room Temperature, and General Amination of Aryl Chlorides at Low Temperatures 212

Contents XI11

7.3.3.1 High-Temperature Aminations Involving P(t-Bu),

7.3.3.2 Use of Sterically Hindered Bisphosphine Ligands 213 7.3.3.2.1 Amination of Aryl Bromides and Chlorides 213 7.3.3.2.2 Amination of Aryl Tosylates 214

as Ligand 212

7.3.3.3 7.3.3.4 7.3.3.5

7.4

7.4.1 7.4.2 7.4.3 7.4.4 7.5 7.6 7.6.1 7.6.1.1 7.6.1.2 7.6.1.3 7.7 7.7.1 7.7.2 7.7.3

7.7.4 7.8 7.8.1

7.8.2 7.8.2.1

7.8.3

7.8.4

7.8.5

7.8.6 7.8.6.1

P,N Ligands and Dialkylphosphinobiaryl Ligands 2 15 Phenyl Backbone-Derived P,O Ligands 216 Low-Temperature Reactions Employing P(t-Bu), as Ligand 217 Aromatic C - N Bond Formation with Non-Amine Substrates and Ammonia Surrogates 219 Amides, Sulfonamides and Carbamates 221 Allylamine as an Ammonia Surrogate 222 Imines 222 Azoles 223 Amination of Base-Sensitive Aryl Halides 226 Applications of the Amination Chemistry 228 Synthesis of Biologically Active Molecules 228 Arylation of Secondary Alkylamines 228 Arylation of Primary Alkylamines 230 Arylation of Primary Arylamines 231 Applications to Materials Science 233 Polymer Synthesis 233 Synthesis of Discrete Oligomers 236 Synthesis of Small Molecules for Materials Applications 239 Palladium-Catalyzed Amination for Ligand Synthesis 240 Mechanism of Aryl Halide Amination and Etheration 241 Oxidative Addition of Aryl Halides to L,Pd complexes (L = P(o-Tolyl),, BINAP, DPPF) and its Mechanism 241 Formation of Amid0 Intermediates 244 Mechanism of Palladium Amide Formation from Amines 244 Reductive Eliminations of Amines from Pd(I1) Amido Complexes 247 Competing (P-Hydrogen Elimination from Amido Complexes 252 Selectivity: Reductive Elimination versus P-Hydrogen Elimination 253 Overall Catalytic Cycle with Specific Intermediates 255 Mechanism for Amination Catalyzed by P(o-C,H,Me), Palladium Complexes 255

XIV Contents

7.8.6.2

7.9 Summary 257 Acknowledgments 258 References 258

Mechanism for Amination Catalyzed by Palladium Complexes with Chelating Ligands 256

Index 263

Abbreviations

acac Alloc BINAP BISBI Bn Boc CAN CP CP" CT dba DBAD DBU DCE de DEAD DIAD DMS DPEphos DPPBA

DPPF DPPP DTBAD D'BPF dr ee EWG GPC IPC KDO LDA

DPPe

Acetonylacetate Ally lox ycarbon yl 2,2'-Bis(dipheny1phosphino)- 1,l' -binaphthyl 2,2'-Bis [ (diphenylphosphino)methyl]- 1,l '-biphenyl Benzyl tert-Butoxycarbon y 1 Ceric ammonium nitrate $-C y clopentadien y 1 $-Pentamethyl cyclopentadienyl Chloramine-T 1 3 -Diphenylpenta- 1,4-dien-3-0ne Dibenzyl azodicarboxylate 1,8-Diazabicyclo[S .4.0]undec- 1 -ene 1 ,2-Dichloroethane Diastereomeric excess Azodicarbox ylate Diisopropyl azodicarboxylate Dimethyl sulfide Bis( 2,2'-dipheny1phosphino)diphenylether 2-(Dipheny1phosphino)benzoic acid Bis(dipheny1phosphino)ethane 1,l '-Bis(dipheny1phosphino)ferrocene Bis(dipheny1phosphino)propane Di-tert-butyl azodicarboxylate B i s( di-te rt-buty lphosphino) ferrocene Diastereomeric ratio Enantiomeric excess Electron withdrawing group Gel permeation chromatography Isopinocamphen yl 3-Deoxy-D-manno-octulosonic acid Lithium diisopropylamide

XVI Abbreviations

LiBTOC LiHMDS LUMO MAP Mes

MOP MTPA

NBS NMP NOBIN NOE NPhth Ns PHANEPHOS PTAB PYr QUINAP RAMP rt S A M P TBAF TBS TDCPP

TFAA THF tipt TMP TMSCl TMSCN TMSOTf To1 TPD TPP Ts Ts,O Xantphos

M,

Mw

TeVY

tert-Butyl-N-lithio-N-[@-toluensulfonyl)oxy] carbamate Lithium hexamethyldisilazide Lowest unoccupied molecular orbital 2-Amino-2’ -(diphenylphosphino)- 1,l ’-binaphthyl Mesityl Number average molecular weight 2-Methoxy-2’ -(diphenylphosphino)- 1,l’ -binaphthyl a-Methoxy-a-(trifluoromethy1)phenylacetic acid Molecular weight N-Bromosuccinimide N-Meth y lp yrrolidone 2-Amino-2’-hydroxy- 1,l ’-binaphthyl Nuclear Overhauser effect Phthalimide 4-Nitrobenzy lsulfonyl 4,12-Bis(diphenylphosphino)[ 2.21 -paracyclophane Phenyltrimethylammonium tribromide Pyridine 1 -(2-Diary lphosphino- 1 -naphthy 1)isoquinoline (R)-( +)- 1 -Amino-2-( methoxymethy1)pyrrolidine Room temperature (3-( -)- 1 -Amino-2-(methoxymethyl)pyrrolidine Tetrabutylammonium fluoride tert-Butyldimethylsilyl meso-Tetra-2,6-dichlorophenylporphyrine Terp yridine Trifluoracetic anhydride Tetrahydro furan Triisopropyl thiophenol 5,1Ol15,20-Tetramesitylporphyrine Chlorotrimethylsilane C y anotrimeth ylsilane Trimethylsilyl trifluorometanesulfonate Tolyl 4,4’-Bis( 3-methylphenylpheny1amino)biphenyl 1,5,15,20-Tetraphenylporphyrine anion Toluene-p-sulfony 1 Toluene-p-sulfonyl anhydride 9,9-Dimethyl-4,6-bis( dipheny1phosphino)xanthene

List of Authors

John M. Brown Dyson Perrins Laboratory University of Oxford South Parks Rd. GB-Oxford OX1 3QY England

Erick M. Carreira Laboratory of Organic Chemistry ETH-Centre Universitatstrasse 16 CH-8092 Zurich Switzerland

Elena Fernandez Departament de Quimica Universitat Rovira I Virgili Placa Imperial Tarraco 1 ES-43005 Tarragona Spain

Jean-Pierre Genet Laboratoire de Synthkse SClective Organique et Produits Naturels Ecole Nationale SupCrieure de Chimie de Paris 11, rue Pierre et Marie Curie F-75231 Paris Cedex 05 France

Christine Greck Laboratoire Synthkse, Interactions et Rkactivitk en Chimie Organique et Bioorganique UniversitC Versailles - Saint Quentin en Yvelines 45, avenue des Etats-Unis F-78035 Versailles Cedex France

John F. Hartwig Department of Chemistry Yale University P.O. Box 208107 New Haven, CT 06520-8107 USA

Hitoshi Iikura Laboratory of Organic Chemistry ETH-Centre Universitatstrasse 16

Switzerland CH-8092 Zurich

Karl Anker JGrgensen Center for Metal Calalyzed Reactions Department of Chemistry Aarhus University Langelandsgade 140

Denmark DK-8000 Aarhus C

Mitsuo Komatsu Martin Schultz-Kukula Department of Applied Chemistry Osaka University Universitat Mainz Yamadaoka 2-4, Suita JP-565087 1 Osaka D-55099 Mainz Japan Germany

Institut fur Organische Chemie

Duesbergweg 10- 14

Horst Kunz Heiko Tietgen Institut fur Organische Chemie Universitat Mainz Universitat Mainz Duesbergweg 10- 14 D-55099 Mainz D-55099 Maim Germany Germany

Institut f i r Organische Chemie

Duesbergweg 10- 14

Damien Lavergne Craig S. Tomooka Laboratoire de Synthkse Sklective Orga- nique et Produits Naturels ETH-Centre Ecole Nationale Suphrieure de Chimie

11, rue Pierre et Marie Curie F-75231 Paris Cedex 05 France

Laboratory of Organic Chemistry

Universitatstrasse 16

Switzerland de Paris CH-8092 Zurich

Satoshi Minakata Department of Applied Chemistry Osaka University Yamadaoka 2-4, Suita JP-565087 1 Osaka Japan

1 Modem Allylic Amination Methods

Karl An ke r J$ rg ensen

1.1 Introduction

One of the challenges in organic chemistry is to prepare fundamental molecular building blocks which either have distinct important properties, or can be used for further transformations in organic synthesis. Ally1 amines 1 can be used as fundamental building blocks in organic chemistry, and their synthesis is an important industrial and synthetic goal. They can be incorporated in natural products, but often the allyl amine moiety is transfornfed to a range of products by functionalization, reduction or oxidation of the double bond.

1

The synthetic methods for the preparation of allyl amines can be divided into several types of reactions [l]. In the present chaptgr, the focus will be on the formation of allyl amines by reaction of substrates having an allylic bond which can be broken. Two approaches will be covered and these are outlined in Scheme 1 : the first method (a) is the synthesis of allyl amines by nucleophilic allylic substitution of compounds having an allyl functionality; the second method (b) is the direct allylic amination of simple alkenes.

(b) + R’NX - Scheme 1

Other types of allylic amination reactions include a variety of indirect approaches such as reduction of a,p-unsaturated imines and oximes, rearrangement of aziridines, and elimination of water from vicinal amino alcohols. However, these reactions will not be considered in this chapter [2].

The present chapter on modem allylic amination methods will be restricted mainly to an overview of some of the major developments for the transformation of allylic compounds into allyl amines according to reaction types (a) and (b) in Scheme 1, and an attempt is made to cover the literature up to August 1999.

The reaction type (a) in Scheme 1 for the allylic amination reaction uses substrates which have an allylic C-X (X = heteroatom, halide) bond and is mainly nucleophilic amination of functionalized alkenes, whereas reaction type (b) is a direct allylic amination of an allcene, based on electrophilic amination of nonfunctionalized alkenes and involves a cleavage of a C-H bond.

1.2 Nucleophilic Amination of Functionalized Alkenes

Nucleophilic amination of alkenes functionalized by an allylic C-X (x = hetero- atoms, halides) as outlined in Eq. (1) is a simple and direct procedure for the synthesis of allyl amines, since very efficient methods for the selective allylic h c - tionalization of alkenes are available.

X = heteroatom. halide

1.2 Nucleophilic Amination of Functionalized Alkenes 3

1.2.1 Amination of Ally1 Alcohols

The Mitsunobu reaction is an attractive procedure for the transformation of an allyl alcohol into an allyl amine [3]. The reaction can be carried out under very mild conditions with a variety of amine nucleophiles. Recently, this method has been used for the preparation of configurationally pure primary allyl amine 4 (Q. 2) by the reaction of allyl alcohols 2 with diisopropyl azodicarboxylate (DIAD) and triphenyl phosphine, followed by phthalimide (PhthNH) as the ammonia synthon giving 3 [4]. Reaction of 3 with hydrazine or methyl amine gave allyl amine 4. An advantage of this reaction sequence is the almost complete conservation of alkene geometry, both under the Mitsunobu coupling conditions and after the depro- tection of the amino group. Use of iminocarbonate as the nitrogen nucleophile donor gives a mixture of trans- and cis-products.

DIADPh3P R' HzNNHz

NPhth 76-88 %-

PhthNH

OH 76-98%*

2 3 4

Several examples of reactions of allyl alcohols under Mitsunobu reaction conditions using diethyl azodicarboxylate (DEAD) and triphenyl phosphine giving allyl amines are known. An example is the reaction of the steroid 5 with azide nucleophiles under Mitsunobu reaction conditions, giving the corresponding azide 6 in 63 % yield (Eq. (3)) [5] . The reaction is regioselective with inversion of the configuration and no S,21 substitution is observed.

The nucleophilic addition to allyl alcohols under Mitsunobu reaction conditions is normally regioselective with no allylic rearrangement during the reaction [6].

4 J@rgensen

The Overman rearrangement, a thermal [3,3]-sigmatropic rearrangement of allylic trichloroacetimidates, is an attractive procedure for the preparation of allyl amines from allyl alcohols (Eq. (4)) [7].

3 8

Ph

[3,3]-sigmatropic rearrangement

9

The first step in this reaction is formation of the allyl trichloroacetimide 8 formed from allyl alcohol 3 by reaction with trichloroacetonitrile. The allyl amides 9 are formed by the [3,3]-sigmatropic rearrangement of 8, followed by hydrolysis. The reaction proceeds with good yield for primary and secondary amides; however, for products where the amide nitrogen is bound to a tertiary carbon atom the yields are generally low.

Overman has suggested a cyclic six-membered transition state 10 for the reaction [8]. The experimental result for the formation of substituted alkenes is similar to that observed for other [3,3]-sigmatropic rearrangements. Furthermore, the preferred formation of the trans-isomer of the di- and trisubstituted alkenes is consistent with transition state 10. The activation parameters for the [3,3]-sigmatropic rearrangements are similar to related rearrangement reactions.

10

The rearrangement reaction can be catalyzed by various metal salts, and salts such as homogeneous solutions of palladium(II) and mercury(I1) complexes have emerged as relatively good catalysts [9]. Based on the catalytic properties of soluble palladium(II) salts, attempts to perform enantioselective rearrangement reactions were performed. The used of a cationic palladium catalyst with a chiral nitrogen ligand led to the first enantioselective version of the Overman rearrangement (Eq. (5)) [9]. The [3,3]-sigmatropic rearrangement of 11 catalyzed by the chird palladium complex 13 gave 12 in 69 % yield and up to 55 % enantiomeric excess (ee).


Ar NAr 13

5 mol Yo

11

2 0

12 55 YO ee

The enantioselectivity of the rearrangement reaction of allylic imidates has been improved significantly by the introduction of chiral ferrocenyl oxazoline catalysts such as 14 [ 101. The use of 14 as catalyst for the reaction of a series of different Z- and E-imidates similar to 11 gave the amides in good yield and with ees higher than 90 % for several of the substrates studied and the chiral ferrocenyl oxazoline catalysts are until know the best catalysts for this rearrangement reaction. It is notable that an exchange of the bridging trifluoroacetate group with an iodine-bridging complex leads to a complex which is inactive, while the chloride-bridging complex is a poor catalyst in terms of reaction rate, but gives the same enantioselectivity as 14 [lOa]. Furthermore, it should be pointed out that the ferrocenyl trimethylsilyl substituent is also of utmost importance for the enantioselectivity as the ee of the reaction is reduced significantly by removal of this substituent [ lOa]. Overman et al. have also investigated other planar - chiral cyclopalladated ferrcenyl amines and imines as chiral catalyst for the allylic imindate rearrangement reactions [lob].

14

6 Jgrgensen

Several other chiral ligands have also been introduced for the rearrangement reaction [ 111. The use of a tridenate ligand containing an (R)-phenyloxazoline as the chiral unit gave in combination with palladium(II) up to 83 % ee for one substrate [ 1 la], while Hayashi et al. have investigated the rearrangement reaction catalyzed by a series of different chiral palladium complexes including bisoxazolines and P,N chelating ligands ((S)-(+)-2-(2-diphenylphosphino)phenyl)-4-(benzyl)ox~oline) with the latter giving up to 81 % ee of the allyl amide; however, the yields were often low [ 1 lb].

One problem with the metal-catalyzed Overman reaction is the basicity of the imidates. However, this problem has also been solved be Overman et al. by the introduction of the less basic allylic N-benzoylbenzimidates. The application of these allylic N-benzoylbenzimidates and palladium(II) chloride as the catalyst improved both the yield, selectivity and rate for the formation of the allyl amines [9].

The palladium(I1)-catalyzed rearrangement of allyl imidates for the formation of allyl amines has also been investigated for chiral imidates (Eq. (6)) [12]. The chiral imidate 15 undergoes a palladium(I1)-catalyzed rearrangement to 16, which was applied for the synthesis of (R)-N-(trichloracety1)norleucinol 17 as presented in Eq. (6).

15 16 17

Several applications of the Overman rearrangement for different type of substrates have been published and some examples can be found in [ 131.

1.2.2 Amination of Allyl Halides

The second approach for the nucleophilic amination reactions to be considered here will be reactions of allyl halides and allyl acetates leading to allyl amines. Allyl halides are normally very reactive in S,2 reactions, but the direct coupling of allyl halides with nitrogen nucleophiles has been performed with limited success [4], as di- and trialkylated by products often predominate. The application of the Gabriel synthesis can to a certain extent eliminate the problem with polyalkylation of amines using, e.g., the stabilized phthalimide anion 19 as the nucleophile. The allyl amine 20


can thus be prepared in good yield from alkyl halides 18 by reaction with potassium phthalimide 19 (Eq. (7)) [14].

18 19 20

A problem with the use of the phthalimide anion as the nucleophile is the removal of phthaloyl group from the product [15]. Therefore, several attempts have been made to develop reagents with a more labile protecting group than the phthalimide. Compounds 21 and 22 are among some of the reagents investigated. By application of 21 and 22, better yields of some primary allyl amines were obtained, compared to the traditional method using the phthalimide [16.] The advantage of 21 and 22 as the nitrogen donor for the formation of allyl amines is that the sub- stituents at the nitrogen atom can easily be removed with gaseous hydrogen chloride after alkylation. However, the substrate tolerance is low, and the reagents are somewhat exotic.

3 Eto.P-N-SiMe3 Em’ H

21 22

The use of the stabilized anion of di-t-butyl iminocarbonate ((Boc),NH) 24 is more promising in allylic amination reaction. It reacts under mild conditions with a variety of primary and secondary halides and mesylates 23, giving the allyl amines 25 in high yields (Eq. (8)) [17]. The use of 24 as the nitrogen donor in the amination reaction has the great advantage compared to the palladium-catalyzed amination with the same reagent, that cis-alkenes react without scrambling of the double bond, an important aspect considering the isomerization sometimes observed using palladium-catalyzed substitution.

8 J#rgensen

5 mol % Lil

23 24 25

1.2.2.1 Amination of Ally1 Halides, Acetates, etc. Catalyzed by Metal Complexes

In 1965, Tsuji et al. observed that palladium could catalyze the allylic alkylation reaction [18]. This discovery, which is a very attractive way to expand the scope of the allylic amination reactions mentioned above, has stimulated an intense research in this field, and even though complexes of nickel, platinum, rhodium, iron, ruthenium, molybdenum, cobalt, and tungsten have been found also to catalyze the alkylation, palladium complexes have received by far the greatest attention [19].

As a spin off, the allylic alkylation reaction, allylic amination reactions can now be carried out in high yield and selectivity and the palladium-catalyzed allylic amination reaction is now a cornerstone reaction in organic chemistry [la,19]. The palladium-catalyzed allylic amination is generally accepted to proceed via a palladium R-

allyl complex 27 (Scheme 2). The E-ally1 complex intermediate 27 is formed by a nucleophilic attack on 26 by palladium and in a second step the amine attacks di- rectly the allylic ligand leading to retention of configuration in the product 28 [19c,d]. It has been observed that the unsymmetrical allyl systems are attacked by the amine nucleophile at the less substituted carbon atom, although there have been observations of reactions on nonsymmetrical substrates with low regioselectivity.


26

I

Pd

27

\ / N

* R’J+A2

Pd(O), 28

Scheme 2

In the palladium-catalyzed allylic amination reaction, primary and secondary amines can be used as nucleophiles, whereas ammonia does not react. Therefore, many ammonia synthons have been developed, and a variety of protected primary ally1 amines can now be prepared using azide, sulphonamide, phthalimide, di-t-butyl iminocarbonate ((Boc),NLi), and dialkyl N-(tert-butoxycarbony1)phosphoramide anions as the nucleophile [20]. An example of the use of ((Boc),NLi) 30 as the amine nucleophile in the palladium-catalyzed allylic amination reaction is shown in Eq. (9). This reaction also illustrates the problem with the regioselectivity in the reaction as a mixture of the products 31-33 are obtained [21].

4 mol % Pd(dba)2 5.5 mol Yo diphos

-oAc + (BOC)# Li’ *

29 30

(9 )

31 32 40 % 47 %

33 7 Yo

modern amination methods - startseite · 4.2.1 syntheses of enantiomerically pure a-amino acids 106...

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