Organometallic Chemistry in Industry

A Practical Approach

Thomas J. Colacot, Carin C.C. Johansson Seechurn

• Publisher: Wiley-VCH
• Year: 2020
• Print ISBN: 9783527345175
• eBook ISBN: 9783527819195
• Edition: 1
• Topic: Physical Sciences
• Subtopic: Organic Chemistry

Showcases the important role of organometallic chemistry in industrial applications and includes practical examples and case studies

This comprehensive book takes a practical approach to how organometallic chemistry is being used in industrial applications. It uniquely offers numerous, real-world examples and case studies that aid working R&D researchers as well as Ph.D. and postdoc students preparing to ace interviews in order to enter the workforce. Edited by two world-leading and established industrial chemists, the book covers flow chemistry (catalytic and non-catalytic organometallic chemistry), various cross-coupling reactions (C-C, C-N, and C-B) in classical batch chemistry, conjugate addition reactions, metathesis, and C-H arylation and achiral hydrogenation reactions.

Beginning with an overview of the many industrial milestones within the field over the years, Organometallic Chemistry in Industry: A Practical Approach provides chapters covering: the design, development, and execution of a continuous flow enabled API manufacturing route; continuous manufacturing as an enabling technology for low temperature organometallic chemistry; the development of a nickel-catalyzed enantioselective Mizoroki-Heck coupling; and the development of iron-catalyzed Kumada cross-coupling for the large scale production of Aliskiren intermediates. The book also examines aspects of homogeneous hydrogenation from industrial research; the latest industrial uses of olefin metathesis; and more.

-Includes rare industrial case studies difficult to find in current literature
-Helps readers successfully carry out their own reactions
-Covers topics like flow chemistry, cross-coupling reactions, and dehydrative decarbonylation
-Features a foreword by Nobel Laureate R. H. Grubbs
-A perfect resource for every R&D researcher in industry
-Useful for PhD students and postdocs: excellent preparation for a job interview

Organometallic Chemistry in Industry: A Practical Approach is an excellent resource for all chemists, including those working in the pharmaceutical industry and organometallics.

1
Industrial Milestones in Organometallic Chemistry

Ben M. Gardner¹, Carin C.C. Johansson Seechurn², and Thomas J. Colacot³

¹Cambridge Display Technology Ltd, Unit 12 Cardinal Park, Cardinal Way, Godmanchester, PE29 2XG, UK

²Johnson Matthey, 28 Cambridge Science Park, Milton Road, Cambridge, CB4 0FP, UK

³Millipore Sigma (A Business of Merck KGAa Darmstadt, Germany), 6000N Teutonia Avenue, Milwaukee, WI 53209, USA

1.1 Definition of Organometallic and Metal–Organic Compounds

Organometallic compounds can be defined as compounds that contain at least one chemical bond between a carbon atom of an organic moiety and a metal. The metal can be alkaline, alkaline earth, transition metal, lanthanide, or a metalloid such as boron, silicon, and phosphorus. Therefore, metal–phosphine complexes are also often included in this category, although they do not contain a typical metal–carbon bond – they are more commonly referred to as “metal–organic compounds.” For the purposes of this book, applications of both organometallic and metal–organic compounds are discussed on the basis of “organometallic chemistry.”

1.1.1 Applications and Key Reactivity

The three major types of applications of organometallic compounds in industry are in the areas of electronics, polymers, and organic synthesis. In organic synthesis, the organometallic compounds are used as either catalysts or stoichiometric reagents.

1.1.1.1 Electronic Applications

For electronic applications typically, the organometallic complex is subjected to chemical vapor deposition (CVD) to form an appropriate thin layer or subjected to organometallic chemical vapor deposition (OMCVD) where the deposition ultimately occurs via a chemical reaction at the substrate surface to produce a high‐quality material. The production of thin films of semiconductor materials is used, for example, for LED applications via metal–organic vapor‐phase epitaxy (MOVPE) where volatile organometallic Me₃E (E = Ga, In, Al, and Sb) compounds are used as precursors. They react with ultrapure gaseous hydrides in a specialized reactor to form the semiconducting product as a crystalline wafer [1–23].

1.1.1.2 Polymers

Another major application for organometallic complexes is in the polymer industry. Three common types of polymers produced via catalysis are particularly noteworthy. Polysiloxanes, also known as silicone, are polymers made up of repeating units of siloxane [4]. They have widespread application in a large number of different fields ranging from cookware to construction materials (e.g. GE silicone), medicine, and toys. Pt‐based catalysts are commonly applied in the silicone industry for the production of a variety of products [5]. A milestone in the history of organometallic chemistry in the industry was the discovery of the Ziegler–Natta catalyst and its application in polymerization reactions [6]. Ziegler and Natta were awarded the Nobel Prize for their work in this field in 1963 [7]. Another area that has been recognized for its importance is olefin metathesis for which a Nobel Prize has been awarded to Grubbs, Schrock, and Chauvin. This has been applied to synthesize polymers via ROMP (ring‐opening metathesis polymerization) [8].

1.1.1.3 Organic Synthesis

The focus of this book, however, is on the exploitation of organometallic compounds for organic synthesis, relevant to industry applications. One of the major applications in organic synthesis is catalysis.

In cases where the organometallic compound is used as a catalyst, for example in a process involving cross coupling, a precatalyst should be able to get activated to the active catalytic species to bind with the organic substrate(s), do the transformation, and release the product such that the active catalytic species returns to its original state in the catalytic cycle. During the organic transformation, the concentration of the catalyst can decrease with time because of poisoning. The efficacy and efficiency of the catalyst depend on how fast and how long it can retain its original activity. The turnover numbers (TONs) and turnover frequencies (TOF) are usually used to describe the activity of a catalyst. Organic chemists have started using organometallic compounds as catalysts to develop more efficient and practical processes [9–12].

The reactivity of organometallic complexes toward various reagents is the reason behind the widespread use of organometallic compounds as catalysts for a variety of organic transformations. The most important types of organometallic reactions are oxidative addition, reductive elimination, carbometalation, hydrometalation, β‐hydride elimination, organometallic substitution reaction, carbon–hydrogen bond activation, cyclometalation, migratory insertion, nucleophilic abstraction, and electron transfer. In the following paragraphs, we will provide a brief overview of the basic theory with some selected applications.

Oxidative addition involves the breakage of a bond between two atoms X–Y. Splitting of H₂ with the formation of two new metal–H bonds is an example of an oxidative addition process (Scheme 1.1). Reductive elimination is the reverse of this process. In an oxidative addition process, the oxidation state of the metal is increased by 2, whereas in reductive elimination, oxidation state of the metal is decreased by 2. Both steps are crucial for metal‐catalyzed cross‐coupling reactions, as the first and the last steps of the catalytic cycle. Several factors can affect these two steps. The structure of the ligand (phosphine or other molecules ...

Table of contents

• Cover
• Table of Contents
• Foreword
• 1 Industrial Milestones in Organometallic Chemistry
• 2 Design, Development, and Execution of a Continuous‐flow‐Enabled API Manufacturing Route
• 3 Continuous Manufacturing as an Enabling Technology for Low‐Temperature Organometallic Chemistry
• 4 Development of a Nickel‐Catalyzed Enantioselective Mizoroki–Heck Coupling
• 5 Development of Iron‐Catalyzed Kumada Cross‐coupling for the Large‐Scale Production of Aliskiren Intermediate
• 6 Development and Scale‐Up of a Palladium‐Catalyzed Intramolecular Direct Arylation in the Commercial Synthesis of Beclabuvir
• 7 Ruthenium‐Catalyzed CH Activated CC/N/O Bond Formation Reactions for the Practical Synthesis of Heterocycles and Pharmaceutical Agents
• 8 Cross‐couplings in Water – A Better Way to Assemble New Bonds
• 9 Aspects of Homogeneous Hydrogenation from Industrial Research
• 10 Latest Industrial Uses of Olefin Metathesis
• 11 Dehydrative Decarbonylation
• Index
• End User License Agreement