SYNTHESIS OF DIVERSE 3-AZIDO-5-(AZIDOMETHYL)BENZENE DERIVATIVES VIA FORMAL C-H AZIDATION AND FUNCTIONAL GROUP-SELECTIVE TRANSFORMATIONS

3-Azido-5-(azidomethyl)benzene derivatives are useful compounds for preparing diverse bistriazole compounds and photoaffinity probes for target identification of bioactive compounds. To more easily synthesize a diverse range of diazido compounds, a facile method for synthesizing diazido compounds bearing a transformable functional group, such as iodo, bromo, methoxycarbonyl, or cyano group, was developed. This method is based on formal C-H azidation of 1,3-disubstituted benzenes via regioselective borylation followed by deborylative azidation, with subsequent transformations, such as that of a one-carbon unit on the benzene ring to an azidomethyl group. The functional groups of the diazido compounds were efficiently transformed to various connecting groups, including carboxy, (succinimidyloxy)carbonyl, hydroxymethyl, formyl, bromomethyl, tosylthiomethyl, ethynyl, diazoacetyl, bromoacetyl, boryl, hydroxy, aminocarbonyl, amino, and isothiocyanato groups, leaving the azido groups untouched. Several diazido building blocks were used to prepare diazido compounds by forming amide, thiourea, and sulfide bonds via conjugation at the connecting groups. These results show that the method described here would facilitate diazido probe syntheses and bistriazole library construction.