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

Abstract

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.

1,3-Di(hetero)aryl-7-substituted Pyrenes—An Undiscovered Area of Important Pyrene Derivatives

“…The possible synthetic routes with feasible reagents and conditions based on literature data are presented in Schemes 1 and 2. As the starting material, commercially available pyrene will be used, which allows obtaining of 1,3-dibromo-7-nitropyrene based on the literature method (Scheme 1) [10,11]. Obtained 1,3-dibromo-7-nitropyrene will be used in the next steps in the synthesis of 1,3-disubstituted by (hetero)aryl groups pyrene derivatives which will be also substituted at position 7 by various groups, as it was mentioned before.…”

Synthetic Protocols for Aromatic Nitration: A Review

“…In addition, this protocol provide efficient route in the synthesis of meta‐nitrated compounds which is difficult to obtain from the existing general method. Form optimistic study authors found that best results obtained in acetonitrile solvent in terms of yield [20] …”

“…Form optimistic study authors found that best results obtained in acetonitrile solvent in terms of yield. [20] Benzothiazole has a prominent place in medicinal chemistry due to its good biological activity and fluorescent properties. Recently Liu and co-workers have developed a new method of nitration of 2-arylbenzothiazoles and arylthiazoles using Ruthenium (Scheme 13).…”

Transition-Metal-Catalyzed Silylation and Borylation of C–H Bonds for the Synthesis and Functionalization of Complex Molecules

“…The telescoped borylation−nitration protocol was applied to the synthesis of the core of nilotinib (Scheme 62). 121…”

“…The one-pot, two-step C−H borylation and nitration presented in Section 3.1.4 of this Review was applied to the nitration of α-tocopherol nicotinate. 121 First, Ir-catalyzed C−H borylation with dtbpy as ligand installed a boronic ester at the C3 position of the pyridine moiety of α-tocopherol nicotinate. In the same pot, the copper-catalyzed nitration furnished the 3nitro derivative of α-tocopherol nicotinate (Scheme 70).…”