Chapter 9
Carbon-Carbon Cross-Coupling
Reactions
9.1 Introduction
Chemical processes have played a vital role in the evolution of human civilization. Catalysts have been known for centuries even before mankind understood
the chemical processes. From the fermentation of wine to vinegar, conversion of
starch to sugar, to the initial industrial application of catalysts to produce sulphuric
acid, catalytic industry has revolutionized our world. They are used in numerous
processes including petrochemical industry for polymerization, oxidation, hydrogenation; production of fertilizers, catalytic convertors in cars, green chemistry;
also, production of drugs in pharmaceutical industry. In this chapter, we will try to
describe the later application that is revolutionizing the health care industry.
Ongoing demand for new drugs and the need to produce drugs at cheaper prices
have stimulated tremendous efforts to develop novel catalysts in pharmaceutical
industry [1]. The diverse materials employed as catalysts include metal oxide, metal
complexes, organic and inorganic polymers, as well as biocatalysts and photocatalysts. An important class of reactions are the transition-metal catalyzed crosscoupling reactions that have wide-ranging applications such as in producing active
pharmaceutical ingredients (API) [2]. As an example, Singulair is an important
drug used for allergies and asthma and is marketed by Merck. Its active ingredient
montelukast sodium requires a Heck reaction using aryl-halide catalyzed by a Pd
catalyst [3–5]. In fact, Pd-catalyzed cross-coupling reactions account for almost
40% of cross-coupling reactions involving C–C bond formation in chemistry and
pharmaceutical industry [6–49]. It is interesting to point out that nickel was used in
cross-coupling reactions in early 1900’s whereas the use of Pd started in 1950’s. One
of the objectives of this chapter is to highlight how recent efforts have led to novel
Pd catalysts used for production of pharmaceuticals and what kind of attempts have
been conducted to replace palladium by cheaper metals. Fundamental information on
the mechanisms underlying metal cluster catalysis is critical to these developments.
© The Editor(s) (if applicable) and The Author(s), under exclusive license
to Springer Nature Singapore Pte Ltd. 2020
Z. Luo and S. N. Khanna, Metal Clusters and Their Reactivity,
https://doi.org/10.1007/978-981-15-9704-6_9
143
Carbon-Carbon Cross-Coupling
Reactions
9.1 Introduction
Chemical processes have played a vital role in the evolution of human civilization. Catalysts have been known for centuries even before mankind understood
the chemical processes. From the fermentation of wine to vinegar, conversion of
starch to sugar, to the initial industrial application of catalysts to produce sulphuric
acid, catalytic industry has revolutionized our world. They are used in numerous
processes including petrochemical industry for polymerization, oxidation, hydrogenation; production of fertilizers, catalytic convertors in cars, green chemistry;
also, production of drugs in pharmaceutical industry. In this chapter, we will try to
describe the later application that is revolutionizing the health care industry.
Ongoing demand for new drugs and the need to produce drugs at cheaper prices
have stimulated tremendous efforts to develop novel catalysts in pharmaceutical
industry [1]. The diverse materials employed as catalysts include metal oxide, metal
complexes, organic and inorganic polymers, as well as biocatalysts and photocatalysts. An important class of reactions are the transition-metal catalyzed crosscoupling reactions that have wide-ranging applications such as in producing active
pharmaceutical ingredients (API) [2]. As an example, Singulair is an important
drug used for allergies and asthma and is marketed by Merck. Its active ingredient
montelukast sodium requires a Heck reaction using aryl-halide catalyzed by a Pd
catalyst [3–5]. In fact, Pd-catalyzed cross-coupling reactions account for almost
40% of cross-coupling reactions involving C–C bond formation in chemistry and
pharmaceutical industry [6–49]. It is interesting to point out that nickel was used in
cross-coupling reactions in early 1900’s whereas the use of Pd started in 1950’s. One
of the objectives of this chapter is to highlight how recent efforts have led to novel
Pd catalysts used for production of pharmaceuticals and what kind of attempts have
been conducted to replace palladium by cheaper metals. Fundamental information on
the mechanisms underlying metal cluster catalysis is critical to these developments.
© The Editor(s) (if applicable) and The Author(s), under exclusive license
to Springer Nature Singapore Pte Ltd. 2020
Z. Luo and S. N. Khanna, Metal Clusters and Their Reactivity,
https://doi.org/10.1007/978-981-15-9704-6_9
143