Pd–Phosphine Precatalysts for Modern Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 101

oxidative addition on to (PR 3 )Pd (DG A ) for several different tertiary phos-
phine ligands were also calculated. It was found that in the R 3 P(R ¼ Me, Et,
i-Pr, t-Bu, Ph) series these values did not change significantly. Importantly,
this means that the reason for the requirement for (t-Bu 3 P)Pd in reactions
with aryl chlorides is not that the oxidative addition is facilitated by the
electron-rich ligand. Instead, through calculations, it was demonstrated that
the dissociation energy (DG d )oft-Bu 3 P from [(t-Bu 3 P) 2 Pd] is significantly
lower than those of the other ligands in the series (R ¼ Me, Et, i-Pr, Ph). In
the case of iodoarenes, however, the oxidative addition is suggested to occur
on to a bisphosphine L 2 Pd(0) because they are more reactive than the other
haloarenes. Typically, C-OTf bonds have similar bond dissociation energy to
C-I, 38 and have been proposed to react preferentially with L 2 Pd(0). 39 The
bromo- and chloroarenes, on the other hand, require the more reactive
monophosphine species [LPd(0)] in order to undergo oxidative addition,
since the C-Br and C-Cl bonds are stronger and more dicult to cleave. 40
The proposal that the catalytically active species is the monophosphine
(L)-based LPd(0) was further supported by the isolation of monomeric three-
coordinate oxidative addition products 1 and 2 by Hartwig and co-workers
(Scheme 3.6). 20 It was shown that these complexes are very likely inter-
mediates in the palladium-catalyzed amination of aryl halides.
Interestingly, the corresponding aryl chloride complexes could not be
isolated from the direct oxidative addition of ArCl to the L 2 Pd(0) catalyst, but
had to be prepared via anion exchange from the LPd(Ar)(Br) complex. 41
These results are consistent with the assumption that palladium catalysts
bearing sterically demanding phosphine ligands favor the formation of
monoligated 12-electron LPd(0) species and are therefore the ligands of
choice for most coupling reactions involving the use of unactivated bromo-
or chloroarenes. When using iodoarenes, aryl triflates or activated bro-
moarenes, less bulky ligands such as Ph 3 P can be employed since the
bisphosphine L 2 Pd(0) is reactive enough for the cross-coupling to take place.
The presence of LPd(0) is suggested to be the reason for the enhanced
reactivity, 42 but the ligand dissociation step is also proposed to be the re-
activity-limiting step. The ligand dissociation can occur by two possible
mechanisms: either via direct ligand dissociation or via substrate-assisted
ligand displacement (Scheme 3.7). 42,43 Computational studies suggest that
the substrate-assisted ligand displacement pathway would be the favored
mechanism. 43
Based on the above studies, a 12-electron-based LPd(0) species is gener-
ated for any bulky phosphine ligand-based Pd complex, although the

I

THF or neat
70°C

Ar
t -Bu 3 P

Pd

ArI ( t -Bu 3 P) 2 Pd

+

1
2

Ar = Ph
Ar = 2,4-xylyl

Scheme 3.6 Investigation into catalytically active species using (t-Bu 3 P) 2 Pd.