Table Of ContentChemical Synthesis Using Highly Reactive Metals
Chemical Synthesis Using Highly
Reactive Metals
Reuben D. Rieke
Copyright © 2017 by John Wiley & Sons, Inc. All rights reserved
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Library of Congress Cataloging‐in‐Publication Data:
Names: Rieke, Reuben D., 1939– author.
Title: Chemical synthesis using highly reactive metals / Reuben D. Rieke.
Description: Hoboken, New Jersey : John Wiley & Sons, Inc., [2017] |
Includes bibliographical references and index.
Identifiers: LCCN 2016034805 | ISBN 9781118929117 (cloth) |
ISBN 9781118929131 (epub) | ISBN 9781118929148 (Adobe PDF)
Subjects: LCSH: Organometallic compounds–Synthesis. | Reactivity (Chemistry)
Classification: LCC QD411.7.S94 R54 2017 | DDC 547/.050453–dc23
LC record available at https://lccn.loc.gov/2016034805
Cover image courtesy: JacobH/Gettyimages
Set in 10/12pt Warnock by SPi Global, Pondicherry, India
Printed in the United States of America
10 9 8 7 6 5 4 3 2 1
v
Contents
Preface xvii
1 Genesis of Highly Reactive Metals 1
2 General Methods of Preparation and Properties 5
2.1 G eneral Methods for Preparation of Highly Reactive Metals 5
2.2 P hysical Characteristics of Highly Reactive Metal Powders 8
2.3 O rigin of the Metals’ High Reactivity 9
R eferences 10
3 Zinc 13
3.1 General Methods for Preparation of Rieke Zinc 13
3.2 D irect Oxidative Addition of Reactive Zinc to Functionalized Alkyl,
Aryl, and Vinyl Halides 16
Typical Preparation of 3‐Fluorobenzylzinc Bromide 19
Typical Preparation of 4‐Cyanobutylzinc Bromide 20
Typical Preparation of 4‐Bromophenylzinc Iodide 20
Typical Preparation of 3‐Methyl‐2‐Pyridlyzinc Bromide 20
3.3 Reactions of Organozinc Reagents with Acid Chlorides 20
Typical Generation of Organozinc Halides from Organic Halides
and Active Zinc and Their Copper‐Mediated Coupling with Acid
Chlorides 21
Synthesis of 4‐Methoxy‐2′‐Thiomethylbenzophenone Using
Tetrakis(triphenylphosphine)palladium(0) as Catalyst 26
Synthesis of Ethyl 7‐(3,4‐Difluorophenyl)‐7‐Oxoheptanoate Using
Copper Iodide as Catalyst 26
Cyanide‐Based Rieke Zinc 27
3.4 R eactions of Organozinc Reagents with α,β‐Unsaturated Ketones 27
Typical Copper‐Mediated Conjugate Addition Reaction
of Organozinc Halides to α,β‐Unsaturated Ketones 30
3.5 R eactions of Organozinc Reagents with Allylic and Alkynyl Halides 30
vi Contents
Typical Reaction of Organozinc Halides
with Allylic Halides 31
Preparation of 2,3‐Di( p‐Cyanobenzyl)‐1,3‐Butadiene
Reaction 34
3.6 Negishi Cross‐Coupling of Vinyl and Aryl
Organozinc Halides 34
Typical Procedure for the Reaction of RZnX
with Aryl and Vinyl Halides 36
Preparation of Aryl Ketones via Ni‐Catalyzed Negishi Coupling
Reactions 36
Typical Reaction Procedure 42
3.7 Intramolecular Cyclizations and Conjugate Additions Mediated
by Rieke Zinc 42
3.8 The Formation and Chemistry of Secondary and Tertiary
Alkylzinc Halides 44
3.9 Electrophilic Amination of Organozinc Halides 50
3.10 Reformatsky and Reformatsky‐Like Reagents and
Their Chemistry 52
Synthesis of Reformatsky Reagent in THF 53
Synthesis of Reformatsky Reagent in Diethyl Ether 53
3.11 Configurationally Stable Organozinc Reagents and Intramolecular
Insertion Reactions 54
3.12 Preparation of Tertiary Amides via Aryl, Heteroaryl, and Benzyl
Organozinc Reagents 55
3.13 Preparation of 5‐Substituted‐2‐Furaldehydes 61
Results and Discussion 63
General Procedure for Pd‐Catalyzed Cross‐Coupling
Reactions 73
3.14 Preparation and Chemistry of 4‐Coumarylzinc Bromide 73
3.15 Preparation and Cross‐Coupling of 2‐Pyridyl and 3‐Pyridylzinc
Bromides 77
Results and Discussion 80
Conclusions 102
Experimental 103
General 103
Preparation of 2‐Pyridylzinc Bromide (P1) 103
Preparation of 3‐Pyridylzinc Bromide (P7) 103
General Procedure for Copper‐Free Coupling Reactions 104
Pd‐Catalyzed Coupling Reaction with
4‐Iodoanisole (10b) 104
Preparation of Bipyridines 104
Pd‐Catalyzed Coupling Reaction with Haloanilines 104
Pd‐Catalyzed Coupling Reactions with Halophenols 105
Copper‐Catalyzed S 2 Addition Reactions 105
N
Pd‐Catalyzed Bimolecular Coupling Reactions 105
Contents vii
Preparation of Quinolinylzinc Reagents and Subsequent Coupling
Reactions 105
3.16 Preparation of Functionalized α‐Chloromethyl Ketones 106
3.17 Rieke Zinc as a Reducing Agent for Common Organic Functional
Groups 108
The General Procedure for Dissolving Zinc Metal Reduction 111
3.18 Detailed Studies on the Mechanism of Organic Halide Oxidative
Addition at a Zinc Metal Surface 111
Results and Discussion 112
Competitive Kinetics 112
Alkyl Bromides 114
Aryl, Vinyl, Benzyl, and Allyl Bromides 114
Stereochemical Studies 117
Radical Detection 119
Mechanistic Considerations 120
Two‐Electron Mechanisms: S 2 121
N
Ate Complex 121
S 1 121
N
One‐Electron Mechanisms 122
Outer‐Sphere Electron Transfer 122
Inner‐Sphere Electron Transfer 122
Linear‐Free Energy Relationships (LFERs) 125
Synthetic Applications 129
Conclusions 130
3.19 Regiocontrolled Synthesis of Poly(3‐Alkylthiophenes) Mediated by
Rieke Zinc: A New Class of Plastic Semiconductors 133
Results and Discussion 136
Regiocontrolled Synthesis of Poly(3-Alkylthiophenes)
Mediated by Rieke Zinc 136
Mechanistic Implications of the Polymerizations 137
Spectroscopic Studies and Other Characterization 139
NMR Spectroscopy 139
Conclusion 143
General Preparation of Regioregular HT Poly(3‐Alkylthiophenes)
from 2,5‐Dibromo‐3‐Alkylthiophenes: Preparation
of Regioregular HT Poly(3‐Hexylthiophene) (4b) 143
General Preparation of Regiorandom Poly(3‐Alkylthiophenes)
from 2,5‐Dibromo‐3‐Alkylthiophenes: Preparation
of Regiorandom Poly(3‐Hexylthiophene) (5b) 144
References 144
4 Magnesium 161
4.1 General Background and Mechanistic Details of Grignard
Reaction 161
General Methods of Metal Activation 164
viii Contents
4.2 General Methods for Preparation of Rieke Magnesium 165
4.3 Grignard Reagent Formation and Range of Reactivity
of Magnesium 167
4.4 1,3‐Diene‐Magnesium Complexes and Their Chemistry 172
Cyclizations of (1,4‐Diphenyl‐2‐butene‐1,4‐diyl)magnesium
with α,ω‐Alkylene Dihalides 173
4.5 Regioselectivity of Reaction of Complexes with Electrophiles 173
4.6 Carbocyclization of (1,4‐Diphenyl‐2‐butene‐1,4‐diyl) magnesium with
Organic Dihalides 175
4.7 1,2‐Dimethylenecycloalkane‐Magnesium Reagents 175
4.8 Synthesis of Fused Carbocycles, β‐γ‐Unsaturated Ketones, and
3‐Cyclopentenols from Conjugated Diene‐Magnesium Reagents 178
4.9 Synthesis of Spiro‐γ‐Lactones and Spiro‐δ‐Lactones from
1,3‐Diene‐Magnesium Reagents 184
4.10 Synthesis of γ‐Lactams from Conjugated Diene‐Magnesium
Reagents 190
4.11 Low‐Temperature Grignard Chemistry 192
Results and Discussion 194
Typical Procedure for the Preparation of the Corresponding
Grignard Reagents 196
4.12 Typical Procedures for Preparation of Active Magnesium and Typical
Grignard Reactions as Well as 1,3‐Diene Chemistry 197
Anhydrous Magnesium Salts 197
Preparation of Rieke Magnesium Using Potassium or Sodium
as Reducing Agent 197
Preparation of a Grignard Reagent Using Rieke Magnesium
Prepared Using Potassium–Potassium Iodide:
1‐Norbornanecarboxyl Acid 199
Preparation of Rieke Magnesium Using Lithium and Naphthalene
as an Electron Carrier 199
Chemistry of (2‐Butene‐1,4‐diyl)magnesium: Preparation
of Activated Magnesium (Mg*) 200
Typical Cyclization of (1,4‐Diphenyl‐2‐butene‐1,4‐diyl)
magnesium 200
Typical Reaction of (2,3‐Dimethyl‐2‐butene‐1,4‐diyl)magnesium 201
Typical Stepwise Reaction of (2,3‐Dimethyl‐2‐butene‐1,4‐diyl)
magnesium 201
Typical Regioselective Reaction of Unsymmetrical (2‐Butene‐1,
4‐diyl)magnesium 202
Typical Reaction of Unsymmetrical (2‐Butene‐1,4‐diyl)magnesium
with SiCl 202
4
Typical Reaction with 1,2‐Dimethylenecyclohexane 202
R eferences 203
Contents ix
5 Copper 209
5.1 Background of Copper and Organocopper Chemistry 209
5.2 Development of Rieke Copper 210
5.3 Phosphine‐Based Copper 211
5.4 Lithium 2‐Thienylcyanocuprate‐Based Copper 220
5.5 Copper Cyanide‐Based Active Copper 224
5.6 Formal Copper Anion Preparation and Resulting Chemistry 228
5.7 Typical Experimental Details of Copper Chemistry 232
Active Copper from CuI and K 232
Reaction of K‐Generated Copper with Pentafluorophenyl
Iodide 233
Preparation of Phosphine‐Based Copper 234
Phosphine‐Based Copper Chemistry 234
Typical Reaction with Acid Chlorides to Form Ketones 234
Typical 1,4‐Addition Reaction with 2‐Cyclohexene‐1‐One 235
Typical Procedure for Intermolecular Epoxide‐Opening
Reaction 235
Typical Procedure for Intramolecular Epoxide‐Opening
Reaction 236
Lithium 2‐Thienylcyanocuprate‐Based
Copper and Chemistry 236
Preparation of Thienyl‐Based Activated Copper 236
Reaction of Organocopper Reagent with Acid Chlorides 237
Epoxide Opening of Organocopper Reagent with 1,2‐
Epoxybutane 237
Copper Cyanide‐Based Active Copper and Chemistry 237
Preparation of Active Copper and Reaction with Organic Halides
to Yield Organocopper Reagents 237
Cross‐Coupling of Benzoyl Chloride with Organocopper Reagents
Derived from CuCN∙2LiBr‐Based Active Copper 237
Conjugate Additions with Organocopper Reagents Derived
from CuCN∙2LiBr‐Based Active Copper 238
Reaction of Allyl Organocopper Reagents Derived from CuCN∙2LiBr
with Benzoyl Chloride 238
Preparation of Copper Anions and Some
Resulting Chemistry 238
Preparation of Cu(−1)Li(+) 238
References 239
6 Indium 241
6.1 Background and Synthesis of Rieke Indium 241
6.2 Preparation of Organoindium Compounds 241
x Contents
The Direct Synthesis of Diphenylindium Iodide and Ditolyindium
Iodide from Activated Indium and Aryl Iodides 243
Results and Discussion 244
6.3 Preparation and Reactions of Indium Reformatsky Reagents 246
6.4 Experimental Details for Preparation and Reactions of Activated
Indium 250
Preparation of Active Indium and Reaction with Alkyl Iodides 250
Reaction of Active Indium with Iodine 250
Triphenylindium 251
Tritolylindium 251
Trimethylindium 251
The Reaction of Activated Indium with Iodobenzene 252
The Reaction of Activated Indium with Iodotoluene 252
The Reaction of Triphenylindium with Iodine 252
Materials 252
Indium Reformatsky Reaction 253
References 253
7 Nickel 255
7.1 P reparation of Rieke Nickel, Characterization of Active Nickel Powder,
and Some Chemistry 255
Preparation of Rieke Nickel Slurries 255
Surface Analysis 256
Discussion 257
Reactions of Slurries 258
Summary 259
Experimental Procedures 259
Preparation of a Typical Nickel Slurry 259
Preparation of Ni(C F ) [P(C H ) ] 260
6 5 2 2 5 3 2
Preparation of Ni(C F ) (C H N) 260
6 5 2 5 5 2
Preparation of Ni(C F ) [(C H ) PH] ∙C H CH 260
6 5 2 6 5 2 2 6 5 3
7.2 Preparation of 3‐Aryl‐2‐hydroxy‐1‐propane by Nickel‐Mediated
Addition of Benzylic Halides to 1,2‐Diketones 261
2‐Hydroxy‐1,2,3‐triphenyl‐1‐propanone (4a: Ar = R1 = R2 = C H ):
6 5
Typical Procedure 265
7.3 P reparation of 3‐Arylpropanenitriles by Nickel‐Mediated Reaction
of Benzylic Halides with Haloacetonitriles 265
Preparation of Metallic Nickel 266
Typical Procedure for 3‐Phenylpropanenitrile (3a) 267
7.4 R eformatsky‐Type Additions of Haloacetonitriles to Aldehydes
Mediated by Metallic Nickel 267
7.5 P reparation of Symmetrical 1,3‐Diarylpropan‐2‐ones from Benzylic
Halides and Alkyl Oxalyl Chlorides 269
Contents xi
7.6 Nickel‐Mediated Coupling of Benzylic Halides and Acyl Halides to Yield
Benzyl Ketones 273
7.7 Nickel‐Assisted Room Temperature Generation and Diels–Alder
Chemistry of o‐Xylylene Intermediates 275
Results and Discussion 277
Typical Preparation of Activated Nickel 282
Reaction of α,α′‐Dibromo‐o‐xylene with Diethyl Fumarate
in the Presence of Metallic Nickel 284
7.8 Active Nickel‐Mediated Dehalogenative Coupling of Aryl and Benzylic
Halides 284
Results and Discussion 285
Results and Discussion 289
Preparation of Activated Nickel Powder 295
Reaction of 4‐Iodomethoxybenzene with Activated Nickel
Powder 296
Trapping of Bis(pentafluorophenyl)nickel(II) Species
with Triphenylphosphine 296
Trapping of (Pentafluorophenyl)nickel(II) Iodide Species
with Triethylphosphine 297
Preparation of Metallic Nickel Powders and Their Reaction with
4‐Nitrobenzyl Chloride 297
References 298
8 Manganese 305
8.1 Preparation of Rieke Manganese 305
8.2 Direct Formation of Aryl‐, Alkyl‐, and Vinylmanganese Halides via
Oxidative Addition of the Active Metal to the Corresponding
Halide 306
8.3 Direct Formation of Organomanganese Tosylates and Mesylates
and Some Cross‐Coupling Reactions 316
8.4 Benzylic Manganese Halides, Sulfonates, and Phosphates : Preparation,
Coupling Reactions, and Applications in New Reactions 320
Introduction 320
Results and Discussion 321
Preparation and Coupling Reactions of Benzylic Manganese
Halides 321
Preparation and Coupling Reactions of Benzylic Manganese
Sulfonates and Phosphates 322
Homocoupling Reactions of Functionalized Benzylic Manganese
Reagents 332
Palladium‐Catalyzed Cross‐Coupling Reactions of Benzylic
Manganese Reagents 335
Limitations of This Approach 335
