meta‐Nitration of Arenes Bearing ortho/para Directing Group(s) Using C−H Borylation

Herein, we report the meta‐nitration of arenes bearing ortho/para directing group(s) using the iridium‐catalyzed C−H borylation reaction followed by a newly developed copper(II)‐catalyzed transformation of the crude aryl pinacol boronate esters into the corresponding nitroarenes in a one‐pot fashion. This protocol allows the synthesis of meta‐nitrated arenes that are tedious to prepare or require multistep synthesis using the existing methods. The reaction tolerates a wide array of ortho/para‐directing groups, such as −F, −Cl, −Br, −CH3, −Et, −iPr −OCH3, and −OCF3. It also provides regioselective access to the nitro derivatives of π‐electron‐deficient heterocycles, such as pyridine and quinoline derivatives. The application of this method is demonstrated in the late‐stage modification of complex molecules and also in the gram‐scale preparation of an intermediate en route to the FDA‐approved drug Nilotinib. Finally, we have shown that the nitro product obtained by this strategy can also be directly converted to the aniline or hindered amine through Baran's amination protocol. A one‐pot method for the meta‐nitration of arenes bearing ortho/para directing group(s) is reported. The method relies on the C−H borylation of the arenes, followed by copper(II)‐catalyzed nitration of the crude ArBpin. This methodology is further extended to π‐electron‐deficient heteroarenes and complex molecules to give synthetically useful nitrated products that normally require multistep synthesis (see scheme).