Direct Arylation via C–H Activation - New Trends in Cross-Coupling: Theory and Applications - page 552

target molecule. 6 One way to impose site selectivity is to exploit the differ-
ences in the electronic environment within the substrate. On the other hand,
introducing directing groups has also helped greatly in solving the riddle of
selective C-H bond activation. In most cases, ortho functionalization has
been observed, 7 but in few instances meta functionalization has also been
achieved. 7,8
The present discussion is mainly focused on recent progress in direct
arylation. Notably, direct alkylation, alkenylation and alkynylation are also
achievable via C-H bond activation catalysts. 9-11 An overview of direct ary-
lation through C-H bond activation under catalysis with various metals such
as Pd, Rh, Ru, Ir and Cu is presented. The literature up to 2013 has been
surveyed for topics related to direct arylation through C-H activation.

12.2 Palladium-Catalyzed Reactions
Transition metal-catalyzed cross-coupling reactions are among the most
popular and convenient routes for making new carbon-carbon and carbon-
heteroatom bonds. The majority of these coupling reactions, including
Suzuki, Heck, Kumada, Stille, Negishi, Hiyama and Buchwald-Hartwig
coupling have utilized Pd catalysts. Although the Kumada reaction was
discovered with Ni 0 , the introduction of Pd by Murahashi's group further
expanded the scope of the reaction. However, these traditional cross-coup-
ling reactions require prefunctionalized substrates. In this context, Pd-
catalyzed direct arylation via C-H activation has recently become one of the
most investigated research topics. The catalytic cycle typically involves the
activation of C-H bonds by a Pd II species, trans-metallation and subsequent
reductive elimination to generate the desired product through C-C bond
formation (Figure 12.1). 12
Pd-catalyzed ligand-assisted C-H functionalization reactions generally
take place at Pd II centers. A palladacycle intermediate is generated, which
can undergo functionalization by two distinct pathways. Functionalization
can occur by reductive elimination or b-hydride elimination involving a
Pd II/0 cycle (Scheme 12.1). Another pathway involves a Pd II/IV cycle where this

sub s t r a t e

substrate R'

RH

RH +base

Pd II Ln

Pd II (OAc) 2

X base induced

C-H activation

oxidant

AcOH

R' X

reoxidation R

oxidative
addition

Pd II

R'

Pd 0 Ln

OAc

Pd II Ln

Pd 0 Ln

R

R' M

R

R' R

trans-metallation

Pd II Ln reductive

elimination

reductive
elimination R'

R' R

Figure 12.1 General mechanism of Pd-catalyzed C-H activation/C-C bond
formation.