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Br
H
Pd(OAc)
2
(10 mol%)
ligand
D
(20 mol%)
KOAc, DMA, 130 °C
olefin (1 equiv), H
2
(1 atm)
Cl
R
O
O
R=Ph,CO
2
t
Bu
Scheme 12.10 Tandem-sequential Heck-direct arylation-hydrogenation.
PdL
n
X
R
k
1
k
-1
and/or
L
n
X
π, η
1
L
n
X
π, η
2
R
R
δ
+
δ
+
k
2
R
R
Pd
Pd
H
H
L
n
L
n
B
X
δ
-
X
δ
-
S
E
3
σ
-
bond metathesis
R
Pd
L
n
+HX
Figure 12.4 Proposed mechanism for Pd-catalyzed intramolecular direct arylation.
kinetic isotope effect of 4.25, excluding the possibility of electrophilic aro-
matic substitution. The presence of a primary kinetic isotope effect can be
rationalized by considering the relative rates of coordination of the arene to
give a p,Z
2
or p,Z
1
complex from the Pd
II
-arene intermediate (k
1
and k
-1
) and
comparing them with the deprotonation step (k
2
). The presence of a primary
KIE implies that k
2
is kinetically significant. Deprotonation can occur in two
ways: either external base deprotonates the arene(via the substitution elec-
trophilic trimolecular or S
E
3 pathway) while the Pd-C bond is forming or
through s-bond metathesis where an anionic ligand on the Pd removes the
proton. It should be noted that s-bond metathesis potentially includes the
concerted metallation-deprotonation (CMD) pathway (Figure 12.4).
12.2.2 Intermolecular Direct Arylation
Fagnou and co-workers reported the direct arylation of electron-deficient
perfluorinated arenes in 2006 (Scheme 12.11).
28
Mechanistic study revealed
that the key C-H bond functionalization step occurs via a concerted
metallation-C-H bond-cleaving process, which depends directly on the
acidity of the C-H bond being cleaved. Two mechanistic pathways were
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