Pd–Phosphine Precatalysts for Modern Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 100

(precatalysts) are easy to handle. In addition, preformed complexes provide
superior results in cross-coupling reactions in comparison with the catalysts
generated in situ using a Pd precursor, such as Pd 2 (dba) 3 or Pd(OAc) 2 (see
Section 3.1 for a discussion on this topic). The following sections describe
the development of the preformed Pd catalysts containing highly active
trialkyl- or aryldialkylphosphine ligands of general formula L 2 Pd(0). Their
excellent performance in a number of cross-coupling reactions is high-
lighted by examples from academia and the pharmaceutical industry.

3.5.1 What is the Catalytically Active Species Formed from
L 2 Pd(0) Complexes?
Generally, in challenging cross-coupling reactions, good results can be
achieved by using sterically demanding ligands in conjunction with a Pd(0)
precursor. It has been shown that the resting state of a catalyst formed in situ
from, for example, Pd 2 (dba 3 ) with the bulky ligand t-Bu 3 P, is L 2 Pd(0). 11
Notably, various deleterious side reactions may take place to produce cata-
lytically inactive species, which diminishes the eciency of the cross-coup-
ling reaction. 32 Until fairly recently, L 2 Pd(0) was also assumed to be the
catalytically active species in a cross-coupling cycle, based on conventional
knowledge. More recent experimental and computational data, however,
support ligand dissociation to LPd(0) and L before oxidative addition of Ar-X
(X ¼ Br or Cl; Figure 3.8). 27,33-35 In addition to this new evidence, there is
increased support for the recent bonding analysis by Landis and Weinhold 36
(see Section 3.2), suggesting the existence of low-ligated Pd species.
The proposal that the monoligated phosphine LPd(0) species is the true
catalytic species has been supported by DFT calculations showing that the
transition states of oxidative addition of PhCl and PhBr to (Ph 3 P) 2 Pd have
higher free energies (DG B ) than the corresponding ones for (Ph 3 P)Pd. 37 The
transition state for (t-Bu 3 P) 2 Pd does not exist. The free energy barriers for

X

Ar

LPd

MeO-C 6 H 4 -X X

L

MeO-C 6 H 4 -X

Ar

LPd

CN-C 6 H 4 -X

CN-C 6 H 4 -X

PdL + L

Δ G B

X
Pd
L

A r
X

Δ G A

LPd

L r

Δ G d

X
Pd
L

L r

PdL 2

bisphosphine pathway monophosphine pathway

X=I

X=Br,Cl

Figure 3.8 Energy barriers in oxidative addition to PdL 2 versus PdL.
Reproduced from Ref. 35.