Pd–Phosphine Precatalysts for Modern Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 92

specific reaction with a concise approach. Whereas the previous chapter
describes the importance of ligands in modern cross-coupling reactions, the
focus of this chapter is geared towards providing insights into how the active
catalytic Pd(0) species is generated from a preformed catalyst for specific
name reactions in cross-coupling.
The way in which L n Pd(0) is generated can significantly affect the overall
rate of the catalytic cycle. If formed in situ, there are a number of deleterious
side reactions that can occur, especially when the new-generation bulky
electron-rich monodentate or electron-rich bidentate ligands with large bite
angles are used. Part of the reasons could be due to the formation of various
L n Pd(0) species. For example, dtbpf (di-tert-butylphosphinoferrocene),
binap [2,2 0 -bis(diphenylphosphino)-1,1 0 -binaphthyl], etc., can form thermo-
dynamically stable, and therefore less reactive, 18-electron species even if the
ratio of Pd to ligand is 1:1. 8,9 When a preformed catalyst is used, the acti-
vation pathway to the catalytically active species will depend not only on its
structure, but also on the nature of the spectator ligands on the Pd. Many of
these pathways are still unknown or speculative; however, some of the recent
studies are encouraging in understanding the structure-activity relationship
(Figure 3.1).
As discussed in the previous chapter, ligands play a significant role in
cross-coupling. Until the mid-90s, Ph 3 P was the most widely used ligand for
palladium-catalyzed coupling reactions, where the substrates were normally
aryl iodides and bromides. Fu and co-workers' pioneering report in 1998 in
line with Koie's work on the use of sterically hindered, electron-rich trialk-
ylphosphine ligands such as t-Bu 3 P and Cy 3 P, along with Buchwald's studies
using dialkylbiarylphosphines, demonstrated the scope of using less reactive
organic chlorides as coupling partners. 10-12 These findings indeed rejuven-
ated the entire area of cross-coupling, making significant advances over the
past 15 years. Figure 3.2 lists some of the most notable P-based ligands for
use in cross-coupling reactions during the last decade. 13 They are all dis-
cussed in more detail in Chapter 2.
In spite of these significant developments, most of the catalyst systems
described above are formed in situ, by mixing a palladium precursor, such as
Pd(dba) x (x ¼ 1.5, 2) or Pd(OAc) 2 , with a ligand. However, dba (dibenzylidene-
acetone) ligand has been reported to retard the activity of the catalyst
significantly when Pd(dba) x is used. 14,15 Also, from a practical point of view,
many of the highly active electron-rich monophosphine ligands are air
sensitive or even pyrophoric (e.g., t-Bu 3 P), which leads to further compli-
cations, especially during reaction scale-up. The problems associated with

L n Pd(0)
n = 1 or 2

PdX n +L n L n PdX n

Figure 3.1 Generation of catalytically active species L n Pd(0) in situ or from

precatalysts.