256
1.2 Challenges in C–H Activation Reactions
However, two major challenges must be conquered in order to develop transition
metal-catalysed C–H activation as a practical tool in organic synthesis. C–H bond is
inert by thermodynamic consideration, so challenging to break, particularly in the
existence of some active functional groups which are higher in reactivity. Taking
into consideration the substantial energies that are essential in regard to direct activation of C–H bonds, one can understand the magnitude of the challenge for these
kinds of transformations. C–H bonds of modest hydrocarbons are most challenging
to activate as they have bond dissociation energies (BDEs) within 96 and 105 kcal/
mol. On the other hand, the BDEs for Me–Cl and Me–Br are 83.7 and 72.1 kcal/
mol, respectively and hence possible to functionalize easily. Besides that, C–H bond
functionalization is also kinetically difficult as compared to other C–X bondbreaking reactions as it does not contain suitable lone pairs for the coordination with
transition metal catalyst [25]. Thus, inertness of C–H bonds become the first challenge. The second challenge is monitoring the site-selectivity. Out of several adjacent C–H bonds with comparable reactivity, functionalizing a specific C–H bond
has long stood as a highly desirable goal.
In order to address the first challenge, various transition metals have been tested
for the reaction with the C–H bonds to establish more labile C–M bonds which
could be further converted into other desired functional groups. Whereas, developing various strategies like the utility of intrinsic electronic nature of substrates [26,
27] and directing groups could be the solution for the second challenge [28, 29].
The catalytic systems for C–H bond functionalization, to be effective by synthesis
point of view, furthermore would have to be (a) stabilized in the existence of the
necessary oxidizing agents, (b) not disabled after coordination of another functional
groups in the target product or solvent, (c) restrictive for a particular kind of C–H
bond in a molecule, and (d) decelerate to catalyse the unnecessary reaction (overoxidation) of the products. The development of novel efficient approaches for
organic synthesis providing a consolidate solution for all these critical challenges
applying mild/green methods is a valuable objective for organic chemistry researchers. On the other hand, the existing worldwide ecological and resource problems are
inspiring for additional investigation and advancement of sustainable
methodologies.
2 C–H Activations Using Heterogeneous Catalysis
Exploiting stoichiometric amount of reagents for organic transformations is now
considered as an old-fashioned strategy. Nowadays, enhanced catalytic systems can
boost the yield of product and reduce the energy and wealth expenditures that add
to raised chemical costs. The last few decades have witnessed the advancement in
the field of catalysis as several highly competent and selective catalysts have been
D. S. Deshmukh et al.
1.2 Challenges in C–H Activation Reactions
However, two major challenges must be conquered in order to develop transition
metal-catalysed C–H activation as a practical tool in organic synthesis. C–H bond is
inert by thermodynamic consideration, so challenging to break, particularly in the
existence of some active functional groups which are higher in reactivity. Taking
into consideration the substantial energies that are essential in regard to direct activation of C–H bonds, one can understand the magnitude of the challenge for these
kinds of transformations. C–H bonds of modest hydrocarbons are most challenging
to activate as they have bond dissociation energies (BDEs) within 96 and 105 kcal/
mol. On the other hand, the BDEs for Me–Cl and Me–Br are 83.7 and 72.1 kcal/
mol, respectively and hence possible to functionalize easily. Besides that, C–H bond
functionalization is also kinetically difficult as compared to other C–X bondbreaking reactions as it does not contain suitable lone pairs for the coordination with
transition metal catalyst [25]. Thus, inertness of C–H bonds become the first challenge. The second challenge is monitoring the site-selectivity. Out of several adjacent C–H bonds with comparable reactivity, functionalizing a specific C–H bond
has long stood as a highly desirable goal.
In order to address the first challenge, various transition metals have been tested
for the reaction with the C–H bonds to establish more labile C–M bonds which
could be further converted into other desired functional groups. Whereas, developing various strategies like the utility of intrinsic electronic nature of substrates [26,
27] and directing groups could be the solution for the second challenge [28, 29].
The catalytic systems for C–H bond functionalization, to be effective by synthesis
point of view, furthermore would have to be (a) stabilized in the existence of the
necessary oxidizing agents, (b) not disabled after coordination of another functional
groups in the target product or solvent, (c) restrictive for a particular kind of C–H
bond in a molecule, and (d) decelerate to catalyse the unnecessary reaction (overoxidation) of the products. The development of novel efficient approaches for
organic synthesis providing a consolidate solution for all these critical challenges
applying mild/green methods is a valuable objective for organic chemistry researchers. On the other hand, the existing worldwide ecological and resource problems are
inspiring for additional investigation and advancement of sustainable
methodologies.
2 C–H Activations Using Heterogeneous Catalysis
Exploiting stoichiometric amount of reagents for organic transformations is now
considered as an old-fashioned strategy. Nowadays, enhanced catalytic systems can
boost the yield of product and reduce the energy and wealth expenditures that add
to raised chemical costs. The last few decades have witnessed the advancement in
the field of catalysis as several highly competent and selective catalysts have been
D. S. Deshmukh et al.