Direct Arylation via C–H Activation - New Trends in Cross-Coupling: Theory and Applications - page 554

OEt

N

N

H Br N

O
Pd(OAc) 2 ,NEt 3 ,MeCN
150 °C

N

X

X

X=O,NH
15-55% yield

X=O,NH

Scheme 12.3 First example of intramolecular direct arylation.

H

Br

Pd(OAc) 2 ,Na 2 CO 3
DMA, 170 °C

O

O

yield = 50-80%

H

H

Br

Pd(PPh 3 ) 2 Cl 2, Na 2 CO 3
DMA, 160 °C

+

O

O

O

40% 35%

Scheme 12.4 Five- and six-membered ring formation through direct arylation.

OH

O

OH

H Pd(OAc) 2

( o -tolyl) 3 P, Cs 2 CO 3
DMA, 85-115 °C

B r

H

Br

L Pd L

O

O

O

yield 75-96%
six entries

OMe

OMe

H

I Pd(OAc) 2, ( o- tolyl) 3 P, Cs 2 CO 3

DMA, 85-115 °C

O

O

yield < 10%

Scheme 12.5 Intramolecular ortho-arylation of phenols.

Generally, aryl iodides are the best substrates among aryl halides for
transition metal-catalyzed cross-coupling reactions because of facile oxida-
tive addition. 16,23 Surprisingly, when an aryl iodide was reacted in the
presence of Pd(OAc) 2 with ligand E a lower TON (turnover number) was
observed compared with an aryl bromide. Initially the reaction was very fast,
but began to slow at 40% conversion and stopped at 60% conversion. Add-
ition of silver salt resulted in an excellent improvement in the TON, which
indicated that iodide may be inhibiting the reaction (Scheme 12.7). 22 It is
well documented that halides can interact with Pd II complexes to generate
palladate species. 24 The stability of these complexes is greatest with iodide
compared with bromide and chloride. 25 The binding of an iodide to form
palladate species would block an additional coordination site and verify the
arene-Pd interactions (Figure 12.3).
Later, Fagnou and co-workers discovered that intramolecular direct
arylation of halides to form five- and six-membered hetero- and carbocyclic
ring systems could be performed with Pd(OH) 2 /C (Pearlman's catalyst)
(Scheme 12.8). 26 To determine the nature of the active catalyst, the solid