Organometallics in Synthesis

Third Manual

Manfred Schlosser

• Publisher: Wiley
• Year: 2013
• Print ISBN: 9780470122174
• eBook ISBN: 9781118484753
• Edition: 1
• Topic: Physical Sciences
• Subtopic: Industrial & Technical Chemistry

WINNER of the 2013 PROSE Award in Chemistry & Physics This latest edition enables readers to master new classes of organometallic compounds and syntheses

A popular resource used by synthetic organic chemists around the world, this book enables readers to conduct seamless synthetic reactions involving key organometallics. Each reaction is set forth in the book's acclaimed recipe-style format so that readers can easily replicate the results in their own labs. Moreover, each chapter has been written by a world leader in the field of organometallics in organic synthesis. These authors offer hands-on guidance and practical examples illustrating the preparation of organometallics and its application in organic synthesis.

This Third Manual of Organometallics in Synthesis features completely new content and topics, with an eye towards providing researchers with the most useful and practical reference on the synthesis of organometallics. Organized into chapters by type of organometallic compound, the book covers:

• Organoalkali chemistry
• Organomagnesium and organozinc chemistry
• Organosilicon and relating organotin chemistry
• Organoiron chemistry
• Organopalladium chemistry

Within each chapter, readers will find background information to learn more about the class of organometallics as well as mechanistic considerations. The authors thoroughly discuss the various methods of preparing the organometallic compounds presented in the book and outline their uses in synthetic reactions. In addition to current applications, the authors explore future research opportunities for each organometallic class. References at the end of each chapter enable readers to explore all the topics in greater depth.

More and more industrial processes rely on organometallic chemistry. As a result, readers will find this book's step-by-step instructions essential in such fields as natural product synthesis, pharmaceuticals, fine chemicals, biotechnology, polymers, and materials science.

Chapter One

Organoalkali Chemistry

Manfred Schlosser

Institute of Chemical Sciences and Engineering (ISIC-BCh) Swiss Federal Institute of Technology (ETH-EPF) CH-1015 Lausanne, Switzerland

Contents

1 Introduction

2 Coverage

3 Reactions

3.1 Displacement of Metal by Hydrogen

3.1.1 Metalation of Aliphatic or Aromatic Hydrocarbons

3.1.2 Neutralization of Organometallic Intermediates

3.2 Displacement of the Metal by Another Metal or Metalloid

3.2.1 “Uphill” Reactions Generating More Basic Species

3.2.2 “Downhill” Reactions Generating More Electrophilic Species

3.2.3 Ate Complex Chemistry

3.3 Displacement of the Metal by a Heterosubstituent

3.3.1 Nitrogen Displaces the Metal

3.3.2 Phosphorus Displaces the Metal

3.3.3 Oxygen Displaces the Metal

3.3.4 Sulfur Displaces the Metal

3.3.5 Fluorine Displaces the Metal

3.3.6 Chlorine Displaces the Metal

3.3.7 Bromine Displaces the Metal

3.3.8 Iodine Displaces the Metal

3.4 Carbon-Carbon Bond Formation

3.4.1 Alkyl and 2-Alkenyl Halides or Sulfonates

3.4.2 Ring Opening of Cyclic Amines and Ethers

3.4.3 Addition onto Carbon—Carbon Multiple Bonds

3.4.4 Addition onto Heteroconjugated Multiple Bonds

3.4.5 Nucleophilic Substitution of 1-Alkenyl Halides

3.4.6 Nucleophilic Addition onto Arenes and Hetarenes

3.4.7 Substitution of Halo-, Alkoxy-, and Metalloarenes or -hetarenes

3.4.8 Addition onto Nonaromatic Carbon—Nitrogen Multiple Bonds

3.4.9 Addition onto Carbonyl Compounds

3.5 Elimination Reactions

3.5.1 α-Elimination (1,1-Elimination)

3.5.2 β-Eliminations (1,2-Eliminations)

3.5.3 δ- and ζ-Eliminations (1,4- and 1,6-Eliminations)

3.5.4 Eliminations Giving Rise to Strained Multiple Bonds

3.6 Rearrangements

3.6.1 Halide-Displacing Carbon [1.2]-Migrations

3.6.2 Isomerization by from-Carbon-to-Carbon Migration

3.6.3 Isomerization by from-Nitrogen-to-Carbon Migration

3.6.4 Isomerization by from-Oxygen-to-Carbon Migration

3.6.5 Isomerization by from-Sulfur-to-Carbon Migration

3.6.6 Ring Closure of Allylmetals and Ring Opening of Cycloalkylmetals

3.6.7 Epilogue

4 Acknowledgments

5 References

List of Abbreviations

Ar	argon
BNZ	benzene
BOC	tert-butoxycarbonyl
DEE	diethyl ether
El	electrophilic part of a reagent El—X
El—X	electrophilic reagent
eq.	(molar) equivalent
glyme	ethylene glycol dimethyl ether
HEX	hexanes (or petroleum ether of bp ~65 °C)
LIC-KOR	superbasic 1:1 mixture of LiC4H9 and KOC(CH3)3
LIDA	lithium diisopropylamide
LIDMAE	lithium 2-(dimethylamino)ethoxide
LIM-KOR	superbasic mixture of LiCH(CH3)C2H5 and KOC(CH3)3
LIT-KOR	superbasic mixture of LiC(CH3)3 and KOC(CH3)3
LITMP	lithium 2,2,6,6-tetramethylpiperid-1-ide
M-Nu	metal-bearing nucleophile (alkoxide, amide)
Nu	nucleophilic group
NAC-KOR	superbasic 1:1 mixture of LiC4H9 and NaOC(CH3)3
NMR	nuclear magnetic resonance
PMDTA	N,N,N′,N″,N″-pentamethyldiethylenetriamine
PEN	pentanes
R	alkyl or aryl
spec.	specifically (on this or that page)
Sv	solvent
THF	tetrahydrofuran
TOL	toluene
TMEDA	N,N,N′,N′-tetramethylethylenediamine

1 Introduction

Indispensable tools in modern synthesis, organometallic reagents were perceived as exotic rarities half a century ago. What caused this profound change in attitude? The breakthrough event was without doubt the discovery of the ortho metalation of anisole and other heterosubstituted arenes by the pioneering work of Georg Wittig, Henry Gilman, and Charles Hauser. When in 1979, Heinz Gschwend and H. Rodriguez^[1] summarized the progress made in this field, a steadily growing community of disciples in both academia and industry had recognized the potential of the new opportunities and had proliferated the underlying ideas in many directions. However, it needed more to transform episodes into a permanent success story. There are unique features that distinguish the organometallic approach to synthesis from previously existing options and establish it as an alternative or complementary concept.

The most salient particularity is presumably the better polarity balance inherent in reactions of polar organometallics. Saturated aliphatic hydrocarbons are totally inert toward nonradical species, and olefins or arenes are too weakly nucleophilic to combine with anything but the strongest electrophiles. This requires drastic conditions and entails poorly selective processes. In contrast, methyllithium or phenyllithium react smoothly with all kinds of electron-hungry substrates including such “lame ducks” as nitrosyl chloride or mercury acetate. This pronounced nucleophilicity widens the choice of reaction partners almost without any restriction and, as a corollary, ascertains product flexibility. Actually, an alkali metal attached to a carbon skeleton can be viewed like a joker in a card game destined to be traded in against something else.

The regioselective metalation of arenes at a position neighboring a heterosubstituent has been mentioned above. Deviations from the ortho rule do exist but are scarce.^[2-5] The metal can nevertheless be systematically directed to meta or para positions if one resorts to the deployment of protective groups or similar stratagems.^[6] Organometallics enable regiocontrol also in the alkenyl series. The addition of bromine onto the double bond of ω-chlorostyrene and subsequent base-mediated dehydrobromination unselectively produces a (Z/E) mixture of 1-bromo-2-chloro-1-phenylethenes. Conversely, the metalation of cis- and trans-ω-chlorostyrene (1-chloro-2-phenylethene) followed by trapping with a source of elemental bromine affords (E)- and (Z)-ω-bromo-ω-chlorostyrene, respectively.^[7] These examples also shine a spotlight on the typoselectivity (or “chemoselectivity”) issue. Whereas ethylene reacts with bromine under addition, vinyllithium undergoes clean substitution. In other words, the organometallic reaction avoids a two-step sequence of consecutive addition and elimination. Such a shortcut often will be welcome.

A widely overlooked aspect of organometallic reactions is their economy. Actually, they are widely considered to be expensive although the price of the reagent is generally negligible. To work at temperatures of liquid ammonia or dry ice has nowada...

Table of contents

• Cover
• Half Title page
• Title page
• Copyright page
• Preface
• Contributors
• Chapter One: Organoalkali Chemistry
• Chapter Two: Organomagnesium and Organozinc Chemistry
• Chapter Three: Organosilicon and Relating Organotin Chemistry
• Chapter Four: Organoiron Chemistry
• Chapter Five: Organopalladium Chemistry
• Index