Metal-free Cross-Dehydrogenative
Coupling of <i>HN</i>-azoles with α‑C(sp<sup>3</sup>)‑H
Amides via C–H Activation and Its Mechanistic and Application
Studies
A metal-free
one step coupling reaction between various <i>N</i>-azole
rings and diverse α-C(sp<sup>3</sup>)-H containing
amides has been developed under oxidative reaction conditions. Commercially
available tetrabutyl ammonium iodide (TBAI) in the presence of terbutylhydroperoxide
(TBHP), under neat reaction condition, efficiently catalyzed the coupling.
Various azole types, such as 1<i>H</i>-benzotriazoles, 1<i>H</i>-1,2,3-triazoles, 1<i>H</i>-1,2,4-triazoles,
1<i>H</i>-tetrazoles, 1<i>H</i>-pyrazoles, and
1<i>H</i>-benzimidazoles, and α-C(sp<sup>3</sup>)-H
containing amides, such as <i>N</i>,<i>N</i>-dimethylacetamide, <i>N</i>,<i>N</i>-dimethylbenzamide, <i>N</i>-methylacetamide, <i>N</i>,<i>N</i>-diethylacetamide, <i>N</i>-methylpyrrolidine, and pyrrolidine-2-one, were successfully
employed for the coupling. A series of designed and controlled experiments
were also performed in order to study the involvement of the different
intermediates. Based on the evidence, a plausible mechanism is also
proposed. These novel, simple, rapid, attractive, and straightforward
transformations open the way of the construction of novel highly functionalized <i>N</i>-azoles via direct covalent N–H bond transformations
onto N–C bonds. This approach allows to the synthesis of complex
molecules requiring number of steps using classical synthetic ways.
In addition, the range of α-C(sp<sup>3</sup>)-H containing amide
substrates is virtually unlimited highlighting the potential value
of this simple system for the construction of complex heterocyclic
molecules, such as fused azoles derivatives