Direct Arylation via C–H Activation - New Trends in Cross-Coupling: Theory and Applications - page 599

DG
C

Ir III visible

light

Pd IV
Ar

DG CH

Ir II I *

ArI +
Ar CAr

DG

+
H +

Ir IV

DG
C

ArI + Ar

Pd II

DG
C

Pd III
Ar

Ar

Figure 12.25 Mechanistic pathway for the Ir/Pd co-catalyzed direct C-H arylation.

12.6 Copper-Catalyzed Reactions
Transition metal-mediated direct arylation to construct biaryl motifs have
been of significant interest, as by-products arising from prefunctionalized
substrates can be avoided. Among these metals, Pd and Rh have been ex-
tensively used for their superior reactivity, where even relatively inactive
chlorides have been employed as the coupling partners. However, from the
viewpoint of catalyst loading, it would be highly advantageous if these
catalysts could be replaced by first-row transition metals such as Cu. Owing
to its relatively lower toxicity, low cost and ease of handling, significant
attention has recently been focused on the development of Cu-mediated
or -catalyzed C-H activation processes.
To address the regioselectivity issues of C-H activation processes with Cu,
several approaches have been devised utilizing (a) the acidity of C-H bonds
to impose site selectivity, (b) the inherent electronic nature of the substrates
under consideration and (c) directing groups for chelation-assisted C-H
activation.
In 2007, Do and Daugulis first developed a Cu-catalyzed direct C-H aryla-
tion of heterocycles with aryl iodides. 163 Astrongbase(LiO t Bu) was employed
for the deprotonation of benzoxazoles whereas KO t Bu was sucient to achieve
high yields with more acidic imidazoles and triazoles. Similar reactivity was
exhibited with polyfluoroarenes as coupling partners (Scheme 12.92). 164
Do and Daugulis proposed a deprotonation-metallation-transmetallation
sequence to explain the observed reactivity of these C-H bonds with pK a values
below 35 (in DMSO). From preliminary investigations, it was suggested that
base-promoted deprotonation generated an aryllithium intermediate, which
underwent transmetallation with Cu. This aryl-Cu intermediate then reacted
with the iodoarenes to generate the C-C coupled product (Scheme 12.93).
The acidity of C-H bonds and the role of base were extremely important,
as fluorobenzene remained unreacted and significant H-D crossover was
observed under basic conditions with or without Cu. C-H bonds flanked
by two electron-withdrawing groups were preferentially arylated. Notably,
Fagnou and co-workers reported such an observation in the Pd-catalyzed
arylation of polyfluoroarenes and aryl halides in 2006. 28 Moreover, an