269
prominent approach in order to realize the selectivity and controllability in C–H
functionalization is the insertion of a heteroatom-containing neighbouring directing
group (DG) into the substrate. Directing groups not only act as a Lewis base for
coordinating the transition metal [111, 112] but also can lead the metal catalyst to a
desired and precise reactive position out of many available sites and therefore
enhance the selectivity to a great extent [26, 113]. Nevertheless, the application of
DGs still possesses certain shortcomings [114], for instance (1) at the C–H activation step, only directing role is played by the DGs and fragment of it leftovers in the
target molecule, (2) the installation and elimination of the directing group adds to
the total count of operations for the synthesis, and (3) additional modification of the
directing group is ever problematic as well as unreasonable, that mostly restricts the
framework diversification of the desired molecule.
Accordingly, employment of inventive DGs possessing enhanced directing
potentials and so characterizing convenient functional groups that are tuneable and
exhibit higher standards of reactivity and selectivity should be favourable. On the
other hand, regarding the catalytic cycle, it mostly comprises a high-oxidation-state
transition-metals in the form of endorser and produces the anticipated products
along with low-oxidation-state metal species generated by reductive elimination.
Thus, the catalysts need to be regenerated in their active oxidation state. As a consequence of this, a general drawback in most of the transition metal-catalysed C–H
functionalizations is the necessity of an equivalent or excessive amount of external
oxidizing agents. These are mostly toxic metal salts like copper or silver salts, benzoquinone or potassium persulphate which are used for the turnover of the expensive transition-metal catalysts and to sustain the catalytic cycle. For instance,
although conventional cross-coupling/cyclization reactions involving oxidation
were extensively implemented for the formation of numerous heterocyclic compounds, in particular indoles [115], pyrroles [116], pyridines [117], isoquinolines
[118] and isoquinolines [119], the DG performs only a directing function, and an
equivalent quantity of external oxidizing agents is necessary in order to regenerate
the catalysts. This creates an equivalent quantity of unwanted side products and offcycle side reactions which obviously provides lower atom economy and reduces the
total ‘greenness’ of the procedure. In the oxidative ruthenium-catalysed C–H annulation methodologies, air or molecular oxygen has even utilized as the oxidizing
agent in the last few years [120, 121]. Thus, in the interest of conquering the shortcomings established by the external oxidizing agents, it would be superlative to
endorse a technique for synthesis consisting ease, security, and environmental
benignity along with superior selectivity as well as variety. The advancement of
multiple role DGs could be among the best solutions to tackle this problem.
In order to regenerate the active transition-metal catalyst, a novel strategy was
pioneered effectively by the researchers like Hartwig [122], Yu [123], Glorius [124],
Guimond and Fagnou [125, 126] and Ackermann [127] individually. The employment of systems that serve together by means of DG as well as (internal) oxidizing
agent simultaneously is an evolving tactic in the area of C–H functionalization
chemistry [128]. This leads to enhanced levels of reactivity and additionally possesses obvious strengths of selectivity, yield and substrate scope. It also avoids the
Insights into Sustainable C–H Bond Activation
prominent approach in order to realize the selectivity and controllability in C–H
functionalization is the insertion of a heteroatom-containing neighbouring directing
group (DG) into the substrate. Directing groups not only act as a Lewis base for
coordinating the transition metal [111, 112] but also can lead the metal catalyst to a
desired and precise reactive position out of many available sites and therefore
enhance the selectivity to a great extent [26, 113]. Nevertheless, the application of
DGs still possesses certain shortcomings [114], for instance (1) at the C–H activation step, only directing role is played by the DGs and fragment of it leftovers in the
target molecule, (2) the installation and elimination of the directing group adds to
the total count of operations for the synthesis, and (3) additional modification of the
directing group is ever problematic as well as unreasonable, that mostly restricts the
framework diversification of the desired molecule.
Accordingly, employment of inventive DGs possessing enhanced directing
potentials and so characterizing convenient functional groups that are tuneable and
exhibit higher standards of reactivity and selectivity should be favourable. On the
other hand, regarding the catalytic cycle, it mostly comprises a high-oxidation-state
transition-metals in the form of endorser and produces the anticipated products
along with low-oxidation-state metal species generated by reductive elimination.
Thus, the catalysts need to be regenerated in their active oxidation state. As a consequence of this, a general drawback in most of the transition metal-catalysed C–H
functionalizations is the necessity of an equivalent or excessive amount of external
oxidizing agents. These are mostly toxic metal salts like copper or silver salts, benzoquinone or potassium persulphate which are used for the turnover of the expensive transition-metal catalysts and to sustain the catalytic cycle. For instance,
although conventional cross-coupling/cyclization reactions involving oxidation
were extensively implemented for the formation of numerous heterocyclic compounds, in particular indoles [115], pyrroles [116], pyridines [117], isoquinolines
[118] and isoquinolines [119], the DG performs only a directing function, and an
equivalent quantity of external oxidizing agents is necessary in order to regenerate
the catalysts. This creates an equivalent quantity of unwanted side products and offcycle side reactions which obviously provides lower atom economy and reduces the
total ‘greenness’ of the procedure. In the oxidative ruthenium-catalysed C–H annulation methodologies, air or molecular oxygen has even utilized as the oxidizing
agent in the last few years [120, 121]. Thus, in the interest of conquering the shortcomings established by the external oxidizing agents, it would be superlative to
endorse a technique for synthesis consisting ease, security, and environmental
benignity along with superior selectivity as well as variety. The advancement of
multiple role DGs could be among the best solutions to tackle this problem.
In order to regenerate the active transition-metal catalyst, a novel strategy was
pioneered effectively by the researchers like Hartwig [122], Yu [123], Glorius [124],
Guimond and Fagnou [125, 126] and Ackermann [127] individually. The employment of systems that serve together by means of DG as well as (internal) oxidizing
agent simultaneously is an evolving tactic in the area of C–H functionalization
chemistry [128]. This leads to enhanced levels of reactivity and additionally possesses obvious strengths of selectivity, yield and substrate scope. It also avoids the
Insights into Sustainable C–H Bond Activation