Organic Synthesis Using Transition Metals

Roderick Bates

• Publisher: Wiley
• Year: 2012
• ISBN:
  9781118313664
• Edition: 2
• Topic: Physical Sciences
• Subtopic: Industrial & Technical Chemistry

Transition metals open up new opportunities for synthesis, because their means of bonding and their reaction mechanisms differ from those of the elements of the s and p blocks. In the last two decades the subject has mushroomed - established reactions are seeing both technical improvements and increasing numbers of applications, and new reactions are being developed. The practicality of the subject is demonstrated by the large number of publications coming from the process development laboratories of pharmaceutical companies, and its importance is underlined by the fact that three Nobel prizes have been awarded for discoveries in this field in the 21st Century already.

Organic Synthesis Using Transition Metals, 2nd Edition considers the ways in which transition metals, as catalysts and reagents, can be used in organic synthesis, both for pharmaceutical compounds and for natural products. It concentrates on the bond-forming reactions that set transition metal chemistry apart from "classical" organic chemistry. Each chapter is extensively referenced and provides a convenient point of entry to the research literature. Topics covered include:

• introduction to transition metals in organic synthesis
• coupling reactions
• C-H activation
• carbonylative coupling reactions
• alkene and alkyne insertion reactions
• electrophilic alkene and alkyne complexes
• reactions of alkyne complexes
• carbene complexes
• h 3 - or p -allyl -allyl complexes
• diene, dienyl and arene complexes
• cycloaddition and cycloisomerisation reactions

For this second edition the text has been extensively revised and expanded to reflect the significant improvements and advances in the field since the first edition, as well as the large number of new transition metal-catalysed processes that have come to prominence in the last 10 years – for example the extraordinary progress in coupling reactions using "designer" ligands, catalysis using gold complexes, new opportunities arising from metathesis chemistry, and C-H activation – without neglecting the well established chemistry of metals such as palladium.

Organic Synthesis Using Transition Metals, 2nd Edition will find a place on the bookshelves of advanced undergraduates and postgraduates working in organic synthesis, catalysis, medicinal chemistry and drug discovery. It is also useful for practising researchers who want to refresh and enhance their knowledge of the field.

1

Introduction

At irregular intervals, it is announced that organic synthesis is dead, that it is a completed science, that all possible molecules can be made by the application of existing methodology, and that there are no new reactions or methods to discover – everything worth doing has been done. And yet new molecular structures come up to challenge the imagination, most often from nature, and new challenges arise from the demands of society and industry, usually to be more selective, to be more efficient and to be more green. The tremendous progress that has been made in the last few decades, including the hectic period since the first edition of this work appeared, is more than ample to prove the prophecies of doom to be wrong. The art and science of organic synthesis continues to make progress as the new challenges are met. While much of the limelight has been taken up by the expansion of the once small and neglected field of asymmetric organocatalysis, huge progress has also been made in the use of transition metals. The academic and practical significance of this area can be seen by a glance at the list of Nobel prizes for chemistry (even if not all of the laureates had intended to contribute to organic synthesis): Sabatier, shared with Grignard (1912), Ziegler1 and Natta2 (1963), Wilkinson3 and Fischer4 (1973), Sharpless,5 Noyori6 and Knowles7 (2001), Grubbs, Schrock8 and Chauvin9 (2005) and, most recently, Heck, Negishi10 and Suzuki11 (2010).

Advances in the area have not been uniform. With the challenge of greenness, atom economy and sustainability, the most progress has been made in the area of catalysis.12 Progress in the use of stoichiometric transition-metal reagents and with transition-metal complex intermediates has lagged, while progress in catalysis has surged ahead. Four areas of transition-metal chemistry have been at the forefront of recent progress. One is the tremendous advances and applications made in the area of alkene metathesis chemistry and its spin-off fields. What was once a mainstay of the petrochemical industry, but a curiosity to synthetic organic chemistry has become a standard method for carbon–carbon bond formation. New metathesis catalysts continue to open up new possibilities. The second, not unrelated, area is the development of new ligands. At one time, except for asymmetric catalysis, triphenylphosphine was the option as a ligand, with a small number of variants available. Driven by the demand for greater efficiency and wider substrate scope, a myriad of complex ligands is now available. While their initial impact was upon coupling reactions, their influence is spreading to other areas. The emergence of the N-heterocyclic carbene ligands has provided a second stimulus in this area and opened up further opportunities. In addition to more ligands, a greater number of the transition metals are finding applications in organic synthesis. While palladium probably remains the most widely used metal, its “market share” has shrunk, with the increasing use other metals. Most notable is the glittering rise of gold and gold catalysis. The final area had been present in the literature for decades but only took off recently. This is the area of C–H activation, based upon the realization that C–H bonds are not passive spectators, but, with the ability of transition metals to insert into them under mild conditions, are potent functional groups.

This is an area of science that is very much alive and moving forwards. Transition-metal chemistry is not only used for academic purposes, but also in the fine chemicals industry. The reader will find references to these real-life applications in the appropriate chapters.

1.1 The Basics

Why? What is special about the transition metals and the chemistry that we can do using them? What makes metals such as palladium, iron and nickel different from metals such as sodium, magnesium and lithium? The answer lies in the availability of d-orbitals, filled or empty, that have energy suitable for interaction with a wide variety of functional groups of organic compounds. In an important example, transition metals can interact with alkenes. In ordinary organic chemistry, simple alkenes are relatively unreactive, being ignored by almost all bases and nucleophiles, requiring a reactive radical or a strong electrophile or oxidizing agent, such as bromine, ozone or osmium tetroxide (watch out – osmium is a transition metal!). But they coordinate to transition metals and their reactivity changes. An important molecule that has almost no “ordinary” organic chemistry is CO. It is ignored by metal ions such as Na+ and Mg2+, but forms complexes with almost all transition metals and is ubiquitous in transition-metal chemistry. The reactions of CO, catalysed by transition metals, has made it a fundamental C1 building block for both complex molecules and bulk chemicals.

Organometallic chemistry begins with the work of Frankland in the 1840s who made the first organozinc compounds. Grignard's work with organomagnesium compounds rapidly became part of the standard repertoire of organic chemists, and remains there today. The pathway for transition metals was not so smooth and took much longer. Indeed, it followed two tracks. One track was in industry, where the understandable objective is a profitable process even if there is no understanding of what is happening in the mechanistic “black box”. This track produced alkene metathesis and hydroformylation. The other track was in academia, restrained by the need to understand. Alongside the isolation of then unexplainable complexes, such as an ethylene complex of platinum by Danish apothecary Zeise,13 one of the starting points is with Ludwig Mond in the late nineteenth century.14 He serendipitously discovered Ni(CO)4 – an amazing compound in that it is a gas under normal conditions, yet is made from so-solid metallic nickel. In terms of using transition metals for synthetic chemistry, a great advance was by Sabatier at the end of the nineteenth cen...

Table of contents

• Cover
• Title Page
• Copyright
• Dedication
• About the Author
• Preface
• Chapter 1: Introduction
• Chapter 2: Coupling Reactions
• Chapter 3: C–H Activation
• Chapter 4: Carbonylation
• Chapter 5: Alkene and Alkyne Insertion Reactions
• Chapter 6: Electrophilic Alkene and Alkyne Complexes
• Chapter 7: Reactions of Alkyne Complexes
• Chapter 8: Carbene Complexes
• Chapter 9: η3- or π-Allyl Complexes
• Chapter 10: Diene, Dienyl and Arene Complexes
• Chapter 11: Cycloaddition and Cycloisomerization Reactions
• Abbreviations
• Index of Principle Transition Metal Catalysts and Reagents
• Index