Introduction to New Trends in Cross-Coupling - New Trends in Cross-Coupling: Theory and Applications - page 16

The intent of the chapters in this topic is to highlight and discuss the most
recent advances and discoveries within the field of cross-coupling.
Chapter 3 by Carin Johansson Seechurn, Hongbo Li and Thomas Colacot
discusses the advantages of the use of well-defined preformed Pd catalysts in
cross-coupling reactions. This is an area that has only been recognized for its
importance in the past 10 years. 51
Although Chapter 2 briefly touches the subject of ligands other than
phosphine, Chapter 4, by Anthony Chartoire and Steven Nolan, details the
advances in C-X coupling that has been made using NHC (N-heterocyclic
carbene) ligands in conjunction with palladium.
Specific examples of the importance of the structural design of the ligands
and its impact on the outcome of cross-coupling reactions are demonstrated
in Chapter 5 by Mark Stradiotto. Here, selective monoarylation reactions of
amines and carbonyl compounds are discussed.
In addition to more thorough mechanistic investigations and realizations
and the continuous expansion of substrate scope for the named cross-
coupling reactions, there are also examples of novel reactions appearing in
the literature. An example is highlighted and discussed in Chapter 7 by
David Petrone, Christine Le, Stephen Newman and Mark Lautens, where the
recently disclosed Pd(0)-catalyzed carboiodination reaction, a reaction
fundamentally rooted in the Heck reaction, is also discussed.
The importance of cross-coupling reactions is reflected in their
frequent use within the chemical industry. To meet the criteria of the eco-
nomic demands for cheaper and more ecient processes, the challenges
within industry are somewhat different from those met within the academic
community. In recent years, continuous flow technology has provided an
attractive alternative to the more traditional batch preparations usually
carried out in process chemistry. This technology has also reached the field
of cross-coupling, an area which is discussed by Timothy No ¨ l and Volker
Hessel in Chapter 13. The chemical industry is constantly faced with
stricter regulations regarding the environmental impact of the processes
being carried out. Kevin Shaughnessy reviews the area of green chemistry via
cross-coupling reactions in Chapter 14. Javier Magano and Joshua
Dunetz demonstrate in Chapter 15 some recent applications of cross-
coupling reactions in the large-scale synthesis of pharmaceuticals and
showcase the problems encountered in a process chemistry environment.
Chapter 16, authored by Kazunori Koide, highlights the problem with
residual Pd in final APIs (active pharmaceutical ingredients) and discusses
detection methods.
In addition to all the improvements developed to expand the field of cross-
coupling involving the introduction of novel ligands, precatalysts, chemical
engineering designs and ever-more in-depth understanding of reaction
mechanisms, the area continues to grow as challenges in terms of in-
corporating problematic nucleophilic and electrophilic reaction partners are
met with innovative solutions. As an example, shown in Scheme 1.13,
Feringa and co-workers recently demonstrated the previously dicult 52