Water-Mediated ortho-Carboxymethylation of Aryl Ketones under Ir(III)-Catalytic Conditions: Step Economy Total Synthesis of Cytosporones A-C.

An expeditious Ir(III)-catalyzed carboxymethylation of aryl ketone with diazotized Meldrum's acid has been developed in aqueous medium. Flavanone and chromanone were also found to be facile substrates with the developed catalytic system. Mechanistic studies revealed the active catalytic species and the role of water in the reaction process as hydroxy and proton sources. Employing the developed method, total synthesis of cytosporone A was achieved in two steps and that of cytosporones B-C was achieved in three steps starting from resorcinol.

Total synthesis of the pseudoindoxyl class of natural products.

The pseudoindoxyl sub-structural motif, amongst the large set of the indole class of alkaloids, represents a unique subset of the oxygenated indole class of the alkaloid family. A majority of this class of natural products contains complex bridged/polycyclic scaffolds with interesting biological profiles. They are thus attractive synthetic targets. Starting from 1963, twenty-eight natural products having the pseudoindoxyl scaffold have been isolated, among which the synthesis of 13 natural products has been accomplished. In this review, we highlight the completed as well as the formal total synthesis of the natural products with a spiro-pseudoindoxyl ring, with a focus on their development. The challenges and the future perspective based on the recent developments in the field will also be discussed. We strongly believe that this review will not only update but also attract the attention of researchers in dealing with the synthesis of pseudoindoxyl compounds.

Ir(iii)-Catalyzed [4 + 2] cyclization of azobenzene and diazotized Meldrum's acid for the synthesis of cinnolin-3(2H)-one.

The first report on Ir(iii)-catalyzed C-H alkylation/cyclization of azobenzene with diazotized Meldrum's acid is described for the synthesis of cinnolin-3(2H)-one derivatives under mild conditions. Controlled experiments led to the isolation of intermediate ortho-alkylated product of azobenzene, which was converted to both cinnolin-3(2H)-one-4-carboxylic acid and its ester derivative. Additionally, the iridacyclic complex of azobenzene was isolated and found to be an active intermediate in the catalytic cycle.

Cp*Co(iii)-catalyzed ortho-amidation of azobenzenes with dioxazolones.

Cp*Co(iii)-catalyzed C-H amidation of azobenzene with dioxazolones has been developed. The amidation reaction does not require external oxidants and gives carbon dioxide as the only by-product. Both symmetrical and unsymmetrical azobenzenes were found to undergo amidation smoothly with broad functional group tolerance.

Synthesis of oxindole from acetanilide via Ir(iii)-catalyzed C-H carbenoid functionalization.

Herein we disclose the first report on the synthesis of oxindole derivatives from acetanilide via Ir(iii)-catalyzed intermolecular C-H functionalization with diazotized Meldrum's acid. A broad range of substituted anilides were found to react smoothly under the Ir(iii)-catalytic system to afford the corresponding N-protected oxindoles. The N-protecting groups, such as Ac, Bz or Piv, can be easily removed to furnish the oxindole. Various synthetic applications of the synthesized oxindole were also demonstrated.

Ir(III)-Catalyzed Carbenoid Functionalization of Benzamides: Synthesis of N-Methoxyisoquinolinediones and N-Methoxyisoquinolinones.

A mild and efficient Ir(III)-catalyzed C-H carbenoid functionalization strategy has been developed to access N-methoxyisoquinolinediones and N-methoxyisoquinolinones. The reaction proceeds efficiently in high yield at room temperature over a broad range of substrates without requirement of any additional oxidants or a base.

Ir(III)-Catalyzed Synthesis of Isoquinoline N-Oxides from Aryloxime and α-Diazocarbonyl Compounds.

An efficient Ir(III)-catalyzed C-H activation and annulations of aryloxime with α-diazocarbonyl compounds has been developed for the synthesis of substituted isoquinoline N-oxides. The reaction proceeds under mild atmospheric conditions, without any external oxidants and releases N2 and H2O as the byproducts. In addition, synthetic applications of the N-oxide products have been established by performing further functionalization. An interesting dimeric iridacyclic complex allied through a bis-silver carboxylate bridge has been isolated that efficiently catalyzed the reaction.

Rhodium(III)-catalyzed C-C bond formation of quinoline N-oxides at the C-8 position under mild conditions.

The Rh(III)-catalyzed C-8 selective direct alkylation and alkynylation of quinoline N-oxides has been developed. The reactions proceeded highly efficiently at room temperature over a broad range of substrates with excellent regioselectivity and functional group tolerance. This development demonstrates the synthetic utility of the N-oxide directing group as a stepping stone for remote C-H functionalization of quinolines.

N-Substituted hydroxylamines as synthetically versatile amino sources in the iridium-catalyzed mild C-H amidation reaction.

N-Substituted hydroxylamines such as aroyloxy- or acyloxycarbamates were successfully employed as synthetically versatile amino precursors in the iridium-catalyzed direct C-H amidation of arenes. The reaction proceeds smoothly at room temperature over a broad range of substrates with high functional group tolerance to afford N-substituted arylamine products.

Total synthesis of (-)-isatisine A.

A modular total synthesis of (-)-isatisine A is described in which four consecutive metal-mediated transformations have been employed at the final stage. These include [Pd]-catalyzed Sonogashira coupling, [Pd]-catalyzed nitroalkyne cycloisomerization leading to isatogens, and addition of indoles to isatogens using InCl(3)- and [Rh]-catalyzed oxidative N-heterocyclization of amino alcohol to form the key amide bond. In addition to these, the removal of the protecting groups has also been carried out in a selective fashion employing either catalytic or stoichiometric metal/metal-based reagents.

Divergent Pd(II) and Au(III) mediated nitroalkynol cycloisomerizations.

A new cycloisomerization reaction comprising the simultaneous addition of nitro and alcohol groups across C≡C leading to skeletally diverse small molecules is documented.