Prominent Ligand Types in Modern Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 48

Me Me

Pd(OAc) 2 (0.5 mol %)
Xantphos (1.5 mol %)
NaOtBu

NEt

Br

NEt

N

O

HN

Toluene, 80 °C

NC

PPh 2 PPh 2

93 %

NC

Xantphos

Figure 2.31 Arylation of N-ethylpiperazine using Pd/Xantphos.

2.5 mol % Pd
Xantphos
Cs 2 CO 3
Dioxane, 100 °C

N

Br

O Ph

H 2 N Ph O

t Bu

91 % t Bu

Figure 2.32 Aryl amidation catalyzed by Pd/Xantphos.

In 2000, Yin and Buchwald found that the Pd/Xantphos combination was
generally effective in its ability to catalyze amidation reactions of activated
and electronically neutral aryl halides/triflates with reasonably broad scope
(Figure 2.32). 120
In 2002, they undertook a detailed study of this transformation with the
aim of addressing some of the limitations encountered in their previous
studies. 121 For instance, electron-rich or sterically encumbered aryl halides
were not productive substrates, as also were not sulfonamides or secondary
acyclic amides. Interestingly, it was observed that in the reactions of these
more challenging substrates, aryl group exchange 86,122 became significant
and more rapid catalyst decomposition was observed when the catalyst
loading was increased. Ultimately, they determined that both catalyst load-
ing and reaction concentration must be carefully controlled for the success
of reactions involving challenging substrates; Pd loadings of 1-4 mol% and
concentrations ranging from 0.125 to 0.5 M were required compared with 1-
2 mol% Pd and 1 M concentration for most of the less challenging examples.
During their mechanistic studies on this process, a Pd-Xantphos oxidative
addition complex was prepared by stirring 4-bromobenzonitrile, Pd 2 dba 3
and Xantphos in benzene at room temperature (Figure 2.33). Unexpectedly,
the 31 P NMR spectrum of this complex contained only one singlet at 9.3
ppm, compared with the pair of doublets observed for the analogous
cis-chelated (BINAP)Pd(4-cyanophenyl)Br oxidative addition complex, pro-
viding evidence for a trans-chelated complex. X-ray crystallography was used
to confirm the rare trans-chelation of the bisphosphine. 123
The most striking structural feature of this complex is its extremely large
bite angle (150.71), which is significantly larger than the bite angle of cis-
(Xantphos)Pd(tetracyanoethylene) (104.61), 119 but closer to that of trans-
(Xantphos)Pd(Me)Cl (1531) measured by van Leeuwen and co-workers. 123