Late Stage Azidation of Complex Molecules

Selective functionalization
of complex scaffolds is a promising
approach to alter the pharmacological profiles of natural products
and their derivatives. We report the site-selective azidation of benzylic
and aliphatic C–H bonds in complex molecules catalyzed by the
combination of Fe­(OAc)2 and a PyBox ligand. The same system
also catalyzes the trifluoromethyl azidation of olefins to form derivatives
of natural products containing both fluorine atoms and azides. In
general, both reactions tolerate a wide range of functional groups
and occur with predictable regioselectivity. Azides obtained by functionalization
of C–H and CC bonds were converted to the corresponding
amines, amides, and triazoles, thus providing a wide variety of nitrogen-containing
complex molecules.