Site-selective direct nitration of 2H-indazoles: easy access to 7-nitroindazoles.

A new site-selective methodology for C-H nitration of 2H-indazoles has been accomplished at the C7 position using iron(III) nitrate. This strategy enables practical access to an array of 7-nitroindazoles with broad functional group tolerance in good yields. The synthesized products have been proven as valuable synthetic intermediates by demonstrating the synthetic utility. Mechanistic investigations indicate that the reaction goes through a radical pathway.

Iodine(III)-promoted oxidative carbotrifluoromethylation of maleimides with imidazopyridines and Langlois' reagent.

A metal-free protocol for oxidative carbotrifluoromethylation of maleimides with imidazopyridines and Langlois' reagent has been developed using (diacetoxyiodo)benzene (PIDA) as an oxidant. This three-component strategy enables one-step construction of 3,4-disubstituted maleimides in good yields with high functional group tolerance. Both experimental and theoretical studies support the proposed radical reaction mechanism.

Skeletal Editing through Molecular Recombination of 2H-Indazoles to Azo-Linked-Quinazolinones.

A new protocol by the combinatory use of two equivalent of indazoles starting material with one being the carbon source via its C3-reactivity and the other, the coupling partner has been developed for the selectfluor-mediated single atom skeletal editing of 2H-indazoles. The azo-linked-2,3-disubstituted quinazolin-4-one derivatives were obtained through a carbon atom insertion between the two nitrogens of the indazole ring and simultaneous oxidation at C3 position of both indazole moieties. Mechanistic investigations reveal that the amidic carbonyl oxygen of the product is derived from water and the reaction proceeds through in-situ generated N-centred indazolone radical intermediate.

Imino-λ3-iodane-Triggered Oxidative Ring-Opening of 2H-Indazoles to ortho-N-Acylsulfonamidated Azobenzenes.

An iminoiodane-enabled oxidative ring-opening of 2H-indazoles via C-N bond cleavage has been developed under metal-free reaction conditions. This methodology afforded a new array of unsymmetrical ortho-N-acylsulfonamidated azobenzenes with a wide functional group tolerance in good yields. The reaction potentially proceeds through the formation of a zwitterionic adduct, which is formed by the reaction between 2H-indazoles and iminoiodane.

Hypervalent iodine(III)-mediated oxidative dearomatization of 2H-indazoles towards indazolyl indazolones.

A new iodine(III)-mediated oxidative dearomatization of 2H-indazoles has been developed to afford N-1 indazolyl indazolones. In this methodology, PIFA plays a dual role: as an oxidant and as a carbonyl oxygen source. A series of indazolone derivatives was promptly synthesized in good to excellent yields through sequential C-heteroatom bond formation. Mechanistic studies indicate that the reaction likely takes place through an SET pathway.

Visible-light-induced Mn(0)-catalyzed direct C-3 mono-, di- and perfluoroalkylation reactions of 2H-indazoles.

A general and efficient method for visible-light-driven fluoroalkylation, such as difluoromethylphosphonation, difluoroacetamidation, monofluoromethylation, difluoromethylation, and perfluoroalkyalation, of 2H-indazoles using an inexpensive Mn2(CO)10 photocatalyst has been developed. The present methodology affords a new series of C-3 fluoroalkylated 2H-indazole derivatives with wide functional group tolerance in good to excellent yields. Difluoromethylenated indiazoles are also prepared from difluoroester derivatives. Our mechanistic investigations support a radical pathway for the reaction.

Remote difunctionalization of 2H-indazoles using Koser's reagents.

A new, efficient, and metal-free protocol has been developed for remote difunctionalization of unreactive C-H bonds at the benzene core of 2H-indazole by employing Koser's reagents, which act as both sulfonyloxylating and iodinating agents under ambient air. The present methodology represents facile access to C-4-sulfonyloxylated and C-7-iodinated 2H-indazole derivatives with high regioselectivity, wide functional group tolerance, and broad substrate scope in good to excellent yields. The formed 4,7 disubstituted 2H-indazoles are the precursors of various C-4,7-functionalized 2H-indazoles through simple transformations.

One-Pot Construction of Indolo[2,3-b]quinoxalines through Ruthenium-Catalyzed Ortho C-H Bond Functionalization of 2-Arylquinoxalines with Sulfonyl Azides.

The synthesis of N-substituted indolo[2,3-b]quinoxalines has been developed through a Ru(II)-catalyzed ortho C-H functionalization of 2-arylquinoxalines with sulfonyl azides and further oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in one pot. This double C-N bond formation strategy provides a new efficient route for the preparation of a series of biologically relevant 6H-indolo[2,3-b]quinoxaline derivatives in up to 94% yield, suggesting a broad substrate scope applicability. The preliminary mechanistic studies reveal that the sequential C-N bond formations proceed through the formation of a five-membered ruthenacyclic intermediate in the first step and a radical mechanism in the second step.

Potassium Persulfate Mediated Chemodivergent C-3 Functionalization of 2H-Indazoles with DMSO as C1 Source.

A facile, efficient, and transition-metal-free chemodivergent C-3 functionalization of 2H-indazoles was developed under aerobic conditions using carboxylic acid and DMSO as the combined source of the carboxylic acid ester group and DMSO as the formylating agent. A series of formylated indazoles and carboxylic acid esters of indazole derivatives were produced in moderate to excellent yields. The mechanistic studies suggest that the reactions probably proceed through a radical pathway.

Ru(II)-Catalyzed Switchable C-H Alkylation and Spirocyclization of 2-Arylquinoxalines with Maleimides via ortho-C-H Activation.

A Ru(II)-catalyzed facile and controllable protocol for C-H alkylation and spirocyclization of 2-arylquinoxalines with maleimides has been achieved under ambient air in high yields. Sequential ortho-C-H activation and C-annulation results in the formation of diverse polyheterocycles containing spiro[indeno[1,2-b]quinoxaline-11,3'-pyrrolidine]-2',5'-diones, which are of potent interest in medicinal chemistry. Mechanistic investigations suggest a reversible cleavage of the ortho-C-H bond in the turnover-limiting step.

Visible light-induced photocatalytic C-H ethoxycarbonylmethylation of imidazoheterocycles with ethyl diazoacetate.

A visible light-mediated regioselective C3-ethoxycarbonylmethylation of imidazopyridines with ethyl diazoacetate (EDA) was achieved under mild reaction conditions. In contrast to the carbene precursors from α-diazoester a first C3-ethoxycarbonylmethylation of imidazopyridines via a radical intermediate has been established. The present methodology provides a concise route to access pharmacologically useful esters with wide functional group tolerance in high yields.