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.

复杂骨架的选择性官能化是改造天然产物及其衍生物药理特性的极具潜力的方法。本研究报道了以Fe(OAc)₂与PyBox配体（PyBox ligand）组合为催化剂，实现复杂分子中苄基与脂肪族C-H键的位点选择性叠氮化反应。该催化体系同样可催化烯烃的三氟甲基叠氮化反应，进而得到同时含有氟原子与叠氮基的天然产物衍生物。总体而言，这两类反应均具有宽泛的官能团耐受性，且可实现可预测的区域选择性。经C-H键与碳碳双键官能化得到的叠氮化物可进一步转化为相应的胺、酰胺与三唑类化合物，由此可获得种类丰富的含氮复杂分子。