A Copper‐Catalyzed Tandem C–H ortho‐Hydroxylation and N–N Bond‐Formation Transformation: Expedited Synthesis of 1‐(ortho‐Hydroxyaryl)‐1H‐indazoles

Abstract

A facile, one‐pot synthesis of 1H‐indazoles featuring a Cu‐catalyzed C–H ortho‐hydroxylation and N–N bond‐formation sequence with the use of pure oxygen as the terminal oxidant was developed. The reaction of readily available 2‐arylaminobenzonitriles with various organometallic reagents led to ortho‐arylamino N–H ketimine species. Subsequent Cu‐catalyzed hydroxylation at the ortho position of the aromatic ring followed by N–N bond formation in DMSO under a pure‐oxygen atmosphere afforded a wide variety of 1‐(ortho‐hydroxyaryl)‐1H‐indazoles in good to excellent yields. This efficient method does not require the utilization of noble‐metal catalysts, elaborate directing groups, or privileged ligands.

Nitrogen–Nitrogen Bond Formation via a Substrate-Bound Anion at a Mononuclear Nickel Platform

“…Many natural products and pharmaceuticals contain N–N bonds, , yet methods to effect N–N bond formation still often invoke highly reactive precursors or intermediates such as azides or nitrenes to proceed . Much interest has been focused on using copper for N–N bond-forming reactions. − …”

3d Transition Metals for C–H Activation

“…The reaction afforded hydroxylated products 1271 in good yields for the reaction of 24 when employing 1.0 equiv of Cu­(OAc) 2 and 1.0 equiv of H 2 O in MeCN under O 2 (1 atm) at 130 °C for 36 h (Scheme b). Related arene acetoxylations/hydroxylations have also been achieved more recently using different heterocycles such as triazole and indazole as the directing groups.…”

Transition‐Metal‐Catalyzed Syntheses of Indazoles

“…Chen, Tang, and co-workers reported Cu-catalyzed sequential CÀ H bond hydroxylation and NÀ N bond formation employing molecular oxygen as the terminal oxidant to construct 1-(ortho-hydroxyaryl)-1H-indazole from ortho-aminoaryl NÀ H ketamines (Scheme 28). [35] ortho-aminoaryl NÀ H ketamines are obtained by the reaction between o-aminobenzonitrile and an organometallic reagent. This o-aminoaryl NÀ H ketamines act as an effective directing group for the cascade CÀ H functionalization/NÀ N bond formation, conserving the nitrogen atoms for the production of 1-(ortho-hydroxyaryl)-1H-indazoles.…”

“…Chen, Tang, and co‐workers reported Cu‐catalyzed sequential C−H bond hydroxylation and N−N bond formation employing molecular oxygen as the terminal oxidant to construct 1‐( ortho ‐hydroxyaryl)‐1 H ‐indazole from ortho ‐aminoaryl N−H ketamines (Scheme ) . ortho ‐aminoaryl N−H ketamines are obtained by the reaction between o ‐aminobenzonitrile and an organometallic reagent.…”