Hydrazo coupling: The efficient transition-metal-free C-H functionalization of 8-hydroxyquinoline and phenol through base catalysis

Article abstract of DOI:10.1039/c9gc02824b

Azodicarboxylate esters are common reagents in organic synthesis laboratories due to their utility in the Mitsunobu reaction. They can also be regarded as possible starting compounds for C-H functionalization, which up until now has been mainly achieved by transition-metal-catalyzed reactions. We have developed a novel reaction involving the quantitative coupling of 8-hydroxyquinoline or phenol with azodicarboxylate esters. The functionalization proceeds under mild base-catalyzed conditions selectively, and either the ortho-position of 8-hydroxyquinoline or para-position of the phenol/naphthol is involved in the reaction. This type of transformation can be considered as "hydrazo coupling" (by analogy with azo coupling). Herein, we discuss a plausible mechanism for this catalyzed substitution, backing up our findings with deuterium NMR experiments and by varying the starting compounds and bases. Using Boc-NN-Boc as a substrate, we have developed the convenient and efficient synthesis of (8-hydroxyquinolin-7-yl)hydrazines, as well as demonstrating a new stereoselective route for the synthesis of medicinally important 4-hydroxyphenylhydrazine for laboratory use, which almost doubles the yield of the common industrial process and reduces the number of synthetic steps. A new "one-pot" procedure for the synthesis of aromatic 8-hydroxyquinolin-7-yl hydrazones was applied.