Prominent Ligand Types in Modern Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 21

systems have been developed utilizing other ligand platforms such as
N-heterocyclic carbenes (NHCs). 4 This chapter focuses primarily on phos-
phine-based systems as Chapter 4 is devoted to cross-coupling reactions with
NHC-based catalysts.
The soft nature of the phosphine is an ideal match for soft low-valent
metals including palladium. According to Crabtree, ''An important part of
the art of organometallic chemistry is to pick suitable spectator ligand sets to
facilitate certain types of reactions'', 5 underlining the importance of ligand
attributes to catalysis. Here, we aim to cover the prominent classes of ligands
that have emerged to generate highly active catalysts in modern Pd-catalyzed
cross-coupling and related processes for broad applications.
2.2 Evolving from Traditional Ligands: the
Significance of Ligand Properties
Owing to its wide availability and ease of handling, early studies on the
development of Pd-catalyzed cross-coupling reactions utilized PPh 3 as the
major supporting ligand. However, in the early 1980s, Heck discovered that a
palladium complex of P(o-tol) 3 (tri-o-tolylphosphine), a ligand more sterically
demanding than PPh 3 , was more active in vinylation reactions in com-
parison with Pd-Ph 3 P complexes, for example, Pd(PPh 3 ) 4 . 6 Furthermore, an
even earlier report in 1979 by Kumada's group revealed a significant
improvement in catalytic activity in the cross-coupling reactions of organo-
bromides with sec-butylmagnesium chloride when a bidentate phosphine
ligand, dppf [1,1 0 -bis(diphenylphosphino)ferrocene], was utilized relative to
a control reaction with PPh 3 . 7 Soon, in an effort to understand these effects
and to design new and improved catalyst systems, chemists began to probe
the effects of ligands in all of the three major steps in cross-coupling
reactions, namely oxidative addition, transmetallation and reductive elim-
ination. Several parameters have since been established to quantify these
properties in order to map their effects on the individual steps of the
catalytic cycle.
Today, the role of the ligand is well understood in terms of steric and
electronic effects, which are often correlated with ''cone angle'' and basicity/
nucleophilicity, respectively. In bidentate ligands, steric properties are
compounded by another effect called the ''bite angle'' effect. The following
sections explain these effects in detail with some theoretical understanding
on the choice of the ligand.
2.2.1 Steric Considerations
Early studies regarding the effects of ligand properties on cross-coupling
reactions were focused primarily on investigating steric considerations. The
steric demand of supporting ligands is significant, as increased bulk pro-
motes ligand dissociation to generate a 12 electron-based monoligated