Direct Arylation via C–H Activation - New Trends in Cross-Coupling: Theory and Applications - page 565

R

R

X

B F 4 - IMesPd(OAc) 2 (5 mol%)

AcOH, 25 °C, 15-24 h

X

+

I +

N

N
R 1

R 1

Me

MeO O 2 N

N
Me

H

N H

Me

89% 58% 70% 67%

Scheme 12.25 Pd-catalyzed 2-arylation of indoles using [Ph 2 I]BF 4 .

Pd I OA c
Ar

Pd I OAc

-Pd 0

Pd(OAc) 2 [Ar 2 I]BF 4

Ar

H

N

N
Me

N
Me

faster
electrophilic
palladation

N
Me

Me

Scheme 12.26 Proposed mechanism of Pd-catalyzed C-arylation of indoles using
[Ar 2 I]BF 4 .

more electron-deficient Pd II catalyst was used. In such a situation, the for-
mation of a s-indole-Pd II complex becomes faster and subsequent arylation
with [Ar-I-Ar]BF 4 occurs via the alternative Pd II /Pd IV cycle (Scheme 12.26). 45
Fagnou and co-workers used p-electron-deficient heterocycles to provide a
synthetically useful method for the preparation of various 2-arylpyridines
and 2-aryldiazines through a Pd-catalyzed coupling of corresponding N-
oxides and aryl halides. 46-50 Both electron-rich and electron-deficient pyri-
dine N-oxides and diazine N-oxides react exclusively at the 2-position. In
addition, the aryl partner tolerated both sterically challenging and elec-
tronically diverse functional groups (Scheme 12.27). The method was also
extended to other azine N-oxides such as quinoline and isoquinoline. 51 In
this context, the use of N-iminopyridinium ylides as an alternative to N-
oxides for analogous C-H arylation should be noted. 52
They carried out experimental and theoretical studies to establish the
mechanism of the direct arylation of different N-oxides. 53 The zero order
with respect to aryl halide suggested a fast oxidative addition of the aryl
halide to Pd 0 , after which the catalyst is saturated as a Pd II species. A 0.5
order with respect to catalyst indicated that the Pd II species could possibly
exist as an inactive dimer that is in equilibrium with the less favored active
monomeric form of the catalyst. Studies with various Pd complexes indi-
cated the involvement of acetate in the transition state as the deprotonating
agent. The reaction likely proceeds via Z 2 -bound acetate on the Pd from
which the pyridine N-oxide can displace one of the acetate oxygens and co-
ordinate to the metal center via ligand substitution. The reaction is then
proposed to proceed through a six-membered CMD transition state, leading
to an Ar 2 Pdbiaryl species that undergoes reductive elimination to provide
the final product and regenerate the Pd 0 catalyst. The carbonate base used
possibly deprotonates the acetic acid generated in this process, providing
the acetate required to continue the catalytic cycle (Figure 12.10). The key