Chapter 1. Suzuki–Miyaura Coupling

The Suzuki–Miyaura coupling (SMC) is the most commonly used carbon–carbon bond forming reaction in the pharmaceutical industry. Its popularity in industry comes from its ability to carry out a wide range of C(sp2)–C(sp2) couplings and to therefore generate a broad range of biaryl motifs in a straightforward manner while displaying a high level of functional group tolerance. The high success rate of the reaction has been driven by the enormous amount of research that has been carried out in developing new ligands and reaction conditions, and it is now the case that the majority of potential substrates can be coupled if the right conditions are chosen. With the huge number of conditions available, the decision as to which to pick with a difficult SMC reaction can be difficult to make. This chapter will detail the best approaches to use for the coupling of challenging substrates as well as highlighting the main issues that can prevent successful reaction. The side reactions encountered with heterocyclic boronates will be discussed in detail and approaches to avoid the issues will be examined. The power of the SMC reaction in allowing selective coupling in dihalogenated systems will also be detailed, and a range of industry examples will be detailed to illustrate the points made.