Preparative Polar Organometallic Chemistry: Volume 1

249 Pages·1987·6.458 MB·English

by  Professor Dr. Lambert Brandsma, Hermann D. Verkruijsse (auth.)

L. Brandsma H. D. Verkruijsse
Preparative
Polar Organometallic
Chemistry
Volume 1
Foreword by Paul von Rague Schleyer
Springer -Verlag
Berlin Heidelberg New York
London Paris Tokyo
Professor Dr. Lambert Brandsma
Hermann D. Verkruijsse
Rijksuniversiteit Utrecht
Organisch Chemisch Laboratorium
Vakgroep Organische Chemie
Padualaan 8, NL-3584 CH Utrecht
ISBN 978-3-540-16916-1 ISBN 978-3-642-87921-0 (eBook)
DOI 10.1007/978-3-642-87921-0
Library of Congress Cataloging in Publication Data
Brandsma, L.
Preparative polar organometallic chemistry.
Bibliography: p.
Includes index.
1. Organometallic chemistry. I. Verkruijsse,
H. D. 11. Title.
QD411.B67 1987 547'.05 86-17896
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© by Springer-Verlag Berlin Heidelberg 1987
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The publisher cannot assume any legal responsibility for given data, especially as far as
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chemicals and laboratory equipment.
Foreword
Polar organometallic compounds are indispensable for the synthetic chemist.
As this book shows, these almost ideal reagents are easy to prepare with high
specificity under mild conditions and yet react quite readily with a great variety
of substrates. Many compounds can be metallated directly at positions which
would otherwise be difficult to substitute. Functional groups and heteroatoms
already present in a molecule direct metallation to sites in their vicinity. The
rules which govern polar organometallic chemistry often are not dominated by
the usual n-delocalization and inductive effects; dipolar interactions, chelation,
polarization, etc. often can be much more important. This affords novel synthetic
opportunities. A good example is the development of a basically new type of
aromatic substitution chemistry not based on positively charged intermediates.
Seebach's injunction, "Thinking of polar organometallic compounds as
carbanions is an impoverishment rather than a simplification" (International
Symposium, Chemistry of Carbanions, Durham 1984), stresses the need to
consider the metal not only as an integral, but perhaps also as the key component
of these reagents. Rather than wandering off as solvated cations and acting as
uninvolved spectators, the metals, rather than the anion moieties, can initiate and
govern the subsequent reactions. To the founders of this field, e.g. Grignard,
Ziegler, Gilman, Wittig, and their followers, the metal was critical. The title of
Schlosser's book, "Polare Organometalle", certainly was apt. If stabilized,
carbanions certainly may be free, but the majority of reagents used synthetically
are based on weak acids. That ion pairs or ion clusters are the reactive inter
mediates, must be appreciated in order to understand this chemistry. Thus, the
accelerating effects of donor solvents, polydentate ligands, and crown ethers is
better attributed, in most instances, to the lowering of the degree of aggregation
rather than to the separation of cation from anion.
The complexity of this chemistry, which we are only now beginning to
understand from a detailed mechanistic viewpoint, is part of its richness. Many
reagents, typically based on lithium, the other alkali metals, or magnesium are
available, sometimes in combination. These reagents may vary greatly in their
effectiveness. The choice of solvents, ligands, and reaction conditions also can be
critical. Success may depend on the design of the experiment, but the literature is
not easily searched. How much better it would be to seek the guidance of experts.
This book provides the examples and the advice one needs.
Laboratory work is Lambert Brandsma's passion. His techniques, developed
over three decades, are not only remarkable in their simplicity, but also in their
effectiveness. Brandsma and his associate, Hermann Verkruijsse, learn more
about the course of a reaction by use of a simple thermometer than most other
chemists with the full array of spectroscopic equipment.
VI Foreword
This series of books are remarkable in documenting the practical knowledge
accumulated through actual personal experience. Each reaction and procedure
has benefited from the critical perspective of the authors. Indeed, "Why run a
reaction for a day when it's over in two minutes?" We learn not only how to
prepare a given compound but, more important, how, in general, polar organo
metallic reactions can be carried out most effectively.
Erlangen, December, 1986 Paul von Rague Schleyer
Preface
The application of organometallic reagents in organic synthesis has a long and
impressive history. During the past ten to fifteen years the significance of the main
group organometallics, in particular of organoalkali and Grignard reagents, has
been augmented by the phenomenal rise of (organo) transition metal compounds
as intermediates in stoichiometric and catalytic processes. The extensive literature
concerning polar organometallic compounds has been summarized in several
review articles and books dealing with various synthetic and more theoretical
aspects.
Nevertheless, the design of appropriate reaction conditions for a particular
synthesis, based on the vast amount of data, remains difficult. Many of the
published procedures are product-directed, which means that the reaction
conditions applied do not always reflect the reactivities of starting compounds
and intermediates. Very low concentrations, in some cases, may be a necessary
requirement for obtaining satisfactory yields, but they are often the natural
consequence of working with small quantities of starting compounds. For
someone who is not familiar with this particular field, but who intends to perform
a reaction on a larger scale, this may lead to an uneconomic use of solvents. Some
procedures do not mention seemingly minor but critical experimental details,
either because the authors do not realize that they could be essential or because
the editors and referees of the particular journal may regard detailed descriptions
unnecessary or undesirable.
The present series, the first volume of which deals with polar organometallic
intermediates derived from sp2-compounds, is intended to be a laboratory manual
for chemistry students at all higher educational levels and for research workers
in industry and universities. The books are a continuation of our series of
manuals in the field of acetylenes and allenes.
A large number of experimental procedures show how polar organometallic
intermediates of the broad spectrum of organic compounds can be generated
and how these can be functionalized with various electrophilic reagents. All
procedures (on the 0.05-0.10 molar scale) have bee preparatively checked in
the laboratory of the authors. The reaction conditions recommended reflect
reactivities of starting compounds and intermediates directly. This may save the
user a considerable amount of time.
The books also contain several variants of known synthetic methods and a
number of practical tips, which have proved their usefulness in the experience of
the authors. Also the indexes guide the user in the selection of the most suitable
conditions for a new metallation-functionalization experiment.
VIII Preface
We are indebted to Dr. A. J. Lawson (Managing Director of the Beilstein
Institut, Frankfurt am Main, FRG) for valuable advice in preparing the
manuscript.
Financial support and gifts of chemical from AKZO Chemie, Deventer,
DSM, Geleen, Dyosynth BV, ass, Oce-Andeno, Venlo and Shell, Amsterdam are
gratefully acknowledged.
Utrecht, December 1986 L.Brandsma
II.D. Verkruijsse
Contents
Introduction to Volume 1 and Instructions for the Use of this Book and its
Indexes. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 1
Chapter I. Organometallic Reagents, Solvents and Laboratory Equipment. 3
1. Strongly Basic Reagents used in Organic Synthesis. . . . . . .. 3
2. Solvents and Some Reagents: Their Analysis, Purification and Storage 6
3. Laboratory Equipment and Some General Remarks Concerning
Performance of the Procedures . . . . . 8
4. Safety, Handling and Methods of Disposal 11
4.1 Introduction . . . . 11
4.2 Organoalkali Reagents 11
4.3 Alkali Metals . . . . 14
4.4 Alkali Metal Amides . 16
5. Experimental Procedures 17
5.1 n-Butyllithium in Diethyl Ether 17
5.2 n-Butyllithium· TMEDA (in Hexane). 18
5.3 n-Butyllithium, Complexed with Potassium t-Butoxide in THF . 18
5.4 n-Butyllithium, Complexed with Sodium-or Potassium t-Butoxide and
TMEDA in Hexane or Pentane . . 19
5.5 Lithium Diisopropylamide . . . . 19
5.6 Lithium Amide in Liquid Ammonia 20
5.7 Sodamide in Liquid Ammonia. . . 21
5.8 Potassium Amide in Liquid Ammonia 22
Chapter II. Reactivity of Polar Organometallic Intermediates 25
1. Introduction . . . . . . . . . . 25
2. General Remarks About Reactivity . . . . . . . . 25
3. Alkylation Reactions. . . . . . . . . . . . . . . 26
3.1 Reactivity of the Various Types of Alkylation Reagents. 26
3.2 Possible Influence of the Thermodynamic Basicity and Polarisability 29
3.3 Reactivity of Some ortho-Lithiated Benzene Derivatives. 30
4. Acylation Reactions . . . . . . . 30
5. Carboxylation. . . . . . . . . . 33
6. Additions to Carbonyl Compounds 34
7. Additions to Heterocumulenes. . . 34
8. Reactions with Sulfenylating Reagents 36
9. Reactions with Elemental Sulfur, Selenium and Tellurium. 37
10. Reactions with Sulfur Dichloride . . . . . . . . . . . 38
x
Contents
11. Trimethylsilylation. . . . . . . . . . . . . 38
12. Introduction of Chlorine, Bromine and Iodine . 38
13. Protonation and Deuteration . . 40
14. Exchange Between Counter Ions ...... . 41
Chapter ill. Metallated OlefInic and Allenic Hydrocarbons 43
1. Deprotonation with Strongly Basic Reagents . . . 43
2. Halogen-Lithium and Tin-Lithium Exchange . . . 45
3. Direct Preparation from Halogen Compounds and Metal 46
4. Experimental Procedures . 47
4.1 Vinylmagnesium Bromide. 47
4.2 Trimethylsilylethene . . . 48
4.3 Tetravinyltin . . . . . . 49
4.4 Reaction of Alkenylmagnesium Bromide with Benzaldehyde . 49
4.5 1-Cyc1ohexenyl- and 1-Cyc1oheptenyllithium. . . . . . . . 50
4.6 1-Cyc1ohexenecarboxaldehyde and 1-Cyc1oheptenecarboxaldehyde 51
4.7 Metallation of Norbornene and Norbornadiene . . . . . . 52
4.8 Norbornadienecarboxaldehyde . . . . . . . . . . . . . . 53
4.9 Reaction of Norbornenyllithium with Methyl Choroformate. . 54
4.10 Metallation of Cyc10pentene and Subsequent Methylthiolation . 54
4.11 2-Hexyl-1-Methylcyc1opropene . . . . . . . . . . . . . . 55
4.12 Lithiation of 1-Methylcyc1opropene and Subsequent Reaction with
Benzaldehyde. . . . . . . . . . . . . . . . . . . . . .. 57
4.13 1,3-Dimetallation of Vinylacetylene and Subsequent Reaction with
two Equivalents of Me SiCI and one Equivalent of n-C HlsBr 58
3 7
4.14 Metallation of Allene with Butyllithium. . 61
4.15 1,2-Decadiene from Allenyllithium. . . . 61
4.16 2,3-Butadienoic Acid from Allenyllithium . 62
4.17 Allenylmagnesium Bromide. . . . . . . 63
4.18 Lithiation of 1.1-Dimethylallene. . . . . 64
4.19 Metallation of 2-Alkynes with Butyllithium 64
4.20 1-Chlorocyc1ohexene and 1-Chlorocyc1oheptene 65
4.21 1-Bromo-2-Mel'hylpropene 66
4.22 Vinylacetylene. . . . 67
4.23 1-Methylcyc1opropene . . 67
4.24 Metallation of Ethene . . 69
4.25 Metallation of Norbornene and Norbornadiene with
BuLi· t-BuOK . TMEDA . 70
4.26 Z-2-Lithio-1-Ethoxyethene 70
4.27 1-Lithio-1-Phenylethene . 72
Chapter IV. Metallation of Hetero-Substituted Unsaturated Systems 75
1. Introduction..................... 75
2. IX-Metallation of 1-Alkenyl Ethers, -Thioethers and Related Systems 76
3. IX-Metallation of 1.3-Dienyl Ethers and -Thioethers . 78
4. IX-Metallated Haloalkenes. . . . . . . . . . . . . . . . . . . 78
Contents XI
5. a-Metallated Allenic Ethers, -Thioethers and -Amines. 79
6. Metallated 1,2,3-Butatrienyl Ethers, -Sulfides and -Amines 82
7. Addendum: Metallation of N,N-Dialkylformamides and
-Thioformamides . . . . . . . 83
8. Experimental Procedures . . . . . . . . . . . . . . 83
8.1 Metallation of Ethyl Vinyl Ether. . . . . . . . . . . 83
8.2 Coupling of Metallated Ethyl Vinyl Ether with Nonyl Bromide
and Acetone . . . . . . . . . . . . . . . . . . . . . 84
8.3 Metallation of 2,3-Dihydrofuran and 2,3-Dihydropyran and
Subsequent Alkylthiolation . . . . . . . . . . . . . . 86
8.4 Metallation of 5-Chloro-2,3-Dihydropyran and Subsequent
Methylthiolation .. . . . . . . . . . . . . . . . . 87
8.5 a-Metallation of Methyl Vinyl Sulfide . . . . . . . . . 88
8.6 Reaction of Metallated Methyl Vinyl Sulfide with Oxirane, Acetone
and Methyl Isothiocyanate . . . . . . . . . . . . . . 89
8.7 Lithiation of Z-1,2-bis (Methylthio)Ethene and Subsequent
Methylation . . . . . . . . . . . . . . . . . . . . 90
8.8 Lithiation of 1,4-Dithiin and Subsequent Functionalization 91
8.9 Metallation of E- and Z-1-Methoxy-1,3-Butadiene and 1-Methylthio-
1,3-Butadiene . . . . . . . . . . . . . . . . . . . . . .. 92
8.10 Metallation of 2H-Thiopyran . . . . . . . . . . . . . . .. 93
8.11 Metallation of E-Dichloroethene and Subsequent Alkylation with
Bromohexane ................... 94
8.12 Conversion of 2-Chloro-1, 1-bis(Dimethylamino) Ethene into
bis(Dimethylamino )Ethyne . . . . . . . . . . . . 95
8.13 Metallation of Methoxyallene . . . . . . . . . . . 96
8.14 Metallation of 1-Alkynyl Sulfides in Organic Solvents 96
8.15 Metallation of Allenic Amines and Acetylenic Amines 97
8.16 Trimethylsilylation of Metallated Diethylaminoallene . 98
8.17 Conversion of a 2-Alkynyl Ether into an 1-Alkylated Allenyl Ether 99
8.18 Conversion of a Tertiary Acetylenic Amine into the Allenic Isomer via
the Metallic Intermediates . . . . . . . . . . . . . . . . . . 100
8.19 Preparation of Dimethylaminobutatriene via the Metallic Intermediate 102
8.20 Preparation of a Metallated Cumulenic Amine via 1,4-Elimination,
and Subsequent Reaction with Trimethy1chlorosilane. . . . . . . 104
8.21 Lithiation of 1-Ethylthio-3-Buten-1-Yne and Subsequent Hydrolysis
to Ethylthiobutatriene . . . . . . 105
8.22 5-Chloro-2,3-Dihydropyran. . . . 106
8.23 Vinyl Alkyl and Vinyl Aryl Sulfides 107
8.24 Z-bis(Methylthio)Ethene . . . . . 108
8.25 2H-Thiopyran. . . . . . . . . . 109
8.26 1, 2-Chloro-1, 1-Bis(Dimethylamino/Ethene 11 0
8.27 3-Methoxy 3-Methyl-1-Butyne and 1-(Dimethylamino)-4-Methoxy-4-
Methyl-2-Pentyne . . . . . . . . . . . . . . . . . . 111
8.28 Lithiation of N,N-Dimethylformamide and N,N-Dimethyl-
thioformamide . . . . . . 112
8.29 N,N-Dimethylthioformamide . . . . . . . . . . . . . 113