Copper‐Promoted Oxidative Intramolecular C–H Amination of Hydrazones to Synthesize 1H‐Indazoles and 1H‐Pyrazoles Using a Cleavable Directing Group

Abstract

A facile and efficient synthesis of 1H‐indazoles and 1H‐pyrazoles through a copper‐promoted oxidative intramolecular C–H amination of hydrazones using a cleavable directing group was developed. This reaction is characterized by its mild conditions, operational simplicity, readily available reagents, and excellent yields. A tentative mechanism for Cu‐mediated C–H oxidative amination was proposed.

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

“…On the other hand, such heterocyclic moieties present in bioactive compounds, or their synthetic intermediates may eventually play the role of a directing group, thus providing an opportunity for convenient and straightforward transformations based on metal-mediated C-H activation [314]. Many methods potentially useful for the synthesis or modification of bioactive compounds based on copper-promoted activation of C-H bonds in (hetero)arenes have been reported in the last years, including methods for the formation of C-C [304][305][306][307][308][309][310][311][312], C-X [315][316][317][318][319], C-N [305,[320][321][322][323][324], C-O [325][326][327][328][329][330], and C-S [324,331,332] bonds. Some of these methods are highlighted herein.…”

“…The copper-mediated C-H activation for C-N bond formation is useful in the synthesis of N-containing heterocycles commonly encountered in bioactive compounds, such as pyrido[1,2a]benzimidazoles [320], 1H-indazoles and 1H-pyrazoles [322], among others. For instance, a method for the modification of 6-anilinopurine nucleosides through copper-mediated C(sp 2 )-H activation and intramolecular amination was reported to synthesize modified nucleosides, which are useful scaffolds in the design of antiviral drugs.…”

Update on the Synthesis of N‐Heterocycles via Cyclization of Hydrazones (2017–2021)

“…[19] Copper-catalyzed intramolecular cyclization of hydrazones with unsaturated bonds has recently been developed widely into one of the most reliable methods of synthesizing nitrogencontaining heterocyclic compounds. [20][21][22] Zora's group first reported using the coppermediated electrophilic cyclization of α,β-alkynic hy-drazones 3 to synthesize a series of pyrazoles 4 (Scheme 1) early in 2011. [23] In this study, α,β-alkynic hydrazone derivatives 3 were prepared efficiently in moderate to excellent yields at 80 °C via condensation of hydrazines 2 with acetylenic aldehydes and ketones 1.…”

Traceless Directing Groups in Sustainable Metal-Catalyzed C–H Activation

“…On the other hand, when the C4 position of the naphthylamide is substituted, the isolated yields are moderate to high for substrates bearing substituents that are electron-donating (117) or electron-withdrawing (118), phenyl groups bearing either electron-withdrawing or -donating moieties (119)(120)(121), naphthyl groups (122), five-membered aromatic rings (123), and a synthetically valuable alkyne unit (124). For compounds having more conjugated systems (125,126), yields are also moderate to high and, significantly, the conditions could be employed for substrates bearing either a quinoline or an isoquinoline unit (127). The versatility of this method is highlighted by a gram-scale preparation for the total synthesis of BET bromodomain inhibitors A and B, which exhibit antitumor and anti-inflammatory activities, via intermediate 115 in two and three steps, respectively.…”

“…Ding and coworkers [125] reported on a facile preparation of 1H-indazoles and 1H-pyrazoles via a Cu-catalyzed intramolecular C-H amination of hydrazones with a 2-amidopyridyne TDG (Scheme 25). These heterocycles are of great interest as they exhibit biological activity, among others encompassing anti-cancer and anti-viral properties.…”