Direct Arylation via C–H Activation - New Trends in Cross-Coupling: Theory and Applications - page 602

12.7 Conclusion
The technique of C-H bond activation as a synthetic tool for the generation
of C-C and C-X bonds has been found to be among the most e cient, mild
and environmentally benign in comparison with more traditional ap-
proaches to the same goals. Transition metals such as Pd, Rh, Ru, Ir and Cu
have been successfully implemented in catalysis. Different ligand scaffolds
have been designed to enhance the catalytic activity. Various directing
groups have also been recognized. However, a few fundamental challenges
remain to be addressed. The presence of directing groups facilitates the
incorporation of the -R group in specific locations, but remains intact in the
product. The perfect approach would be the introduction of -R even in the
absence of the directing group. Alternatively, a traceless moiety incorporated
in the starting material leads to a final product without unwanted append-
ages. A few developments have already been made regarding this issue, 1 but
these approaches are mostly either substrate specific and/or metal specific.
In such an approach, the present challenge relies in developing a truly ef-
ficient system wherein a slight variation in the catalyst or ligand environ-
ment would result selectively in different regioisomers. In the absence of a
directing group, the electronic and steric parameters dominate the select-
ivity. Hence the selectivity found in these cases is mostly complementary to
the directing group-assisted pathways. One particularly attractive option for
improved selectivity will be to incorporate the design elements needed for a
certain molecular recognition into the catalyst scaffolding. This is especially
important for activation of C-H bonds in molecules with no functional
handles. The essential problem illustrated by methane C-H activation is
such a case. 173,174 Despite all these shortcomings, the direct transformation
of C-H to C-C has already enriched the synthetic methodology and further
rapid advances in this area can be expected.
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