Double functionalization of Pyridine as a substance with abundant biological properties

pyridine scaffold one of the most important class of heterocycles, is ubiquitous in a wide variety of organisms and biologically active structures. [1] Many drugs currently on the market contain pyridine core nucleus. Due to the biological properties of pyridine, there have been many reports of the functionalization of these compounds in the last decade. [2] One of the attractive ways to functionalization of different compounds is to use Catellani s strategy. [3] In this approach it is possible to functionalization two positions in a one pot. In this work, this strategy was used to double functionalization of pyridine compounds. 2-iodopyridine derivatives have been used as a source of pyridine. The reaction involves the cyanation of position 2 and the alkylation of position 3 of pyridine. Thus, the process involves coupling to position 2, and C-H activation at position 3. The reaction is carried out in the presence of palladium acetate as a catalyst and the triphenylphosphine as a ligand, and Zn(CN)2 as the cyanide source. The features of this work include the formation of palladacycle as an intermediate for C-H activation of 3-position of pyridine. So, a practical method was proposed for the double functionalization of pyridine in which palladium acetate was used for C-H activation and Zn(CN)2 was used as a cheap and available source for pyridine cyanation. Although norbornene not present in the finished product, its role in the formation of palladacycle and C-H activation of 3-position of pyridine is unavoidable.

Keywords:

Pyridine , cyanation , palladium , catellani reaction