Base-promoted multicomponent synthesis of 1,2,4-triazole-based hybrids from 1,3-diones, ß-nitrostyrenes, and hydrazones.

Herein, we report a metal-free, base-promoted route for the synthesis of hybrid molecular scaffolds in which various 1,3-diones and 1,2,4-triazoles are linked by a benzyl bridge. This three-component, one-pot reaction was accomplished by first treating 4-hydroxycoumarin, trans-ß-nitrostyrene, and aldehyde hydrazone in the presence of sodium carbonate. Further, this protocol was successfully expanded to other 1,3-diones, such as dimedone and 4-hydroxy-2-quinolone. A broad substrate scope, mild reaction conditions, and the metal and ligand/additive-free approach are the prominent features of this strategy.

Copper-catalyzed aerobic annulation of hydrazones with dienones: an efficient route to pyrazole-linked hybrid molecules.

A copper-catalyzed aerobic [3 + 2] annulation reaction to access various pyrazole-bound chalcones starting from readily available and cost-effective hydrazones and dienones is reported. These pyrazole-bound chalcones were further utilized effectively to prepare a series of pyrazole-linked hybrid molecules, such as pyrazole-pyrazoline, pyrazole-aziridine, and pyrazole-pyridine hybrids by efficient simple transformations. Synthetically challenging hybrid molecules were obtained in a simple, two-step process with high atom economy under aerobic copper catalysis.

Metal-Free Bisamidation of N-Tosylhydrazones with Carboxylic Acids Promoted by Tetrabutylammonium Iodide and tert-Butyl Hydroperoxide.

A versatile reaction between N-tosylhydrazones and carboxylic acids to access bisamides is reported. This metal-free, room-temperature reaction was catalyzed by TBAI, while TBHP served as the oxidant. Broad substrate scope and good functional group tolerance are the key features of the strategy. Subsequent intramolecular N-arylation of suitably substituted bisamides readily afforded functionalized 3-indazolones.

Progress in copper-catalysed/mediated intramolecular dehydrogenative coupling.

Transition metal-catalysed C-H functionalization reactions are one of the most efficient synthetic methodologies to construct carbon-carbon and carbon-heteroatom bonds. The initial developments in the field were largely dominated by expensive transition metal catalysts. However, in the past decade, the focus of the catalyst shifted to first-row transition metals and copper catalysis contributed significantly. Abundant, cost-effective, and less toxic copper catalysts are an ideal green alternative to palladium and similar metals. The intramolecular dehydrogenative coupling itself developed as a prominent area of focus as the strategy straightaway affords complex polycyclic scaffolds in one pot. Regioselective activation of inert C-H bonds were made possible with copper catalysts and interestingly, oxygen served as the terminal oxidant in most of the cases. In the present review the focus is on the intramolecular dehydrogenative coupling reactions between carbon-hydrogen and heteroatom-hydrogen bonds to afford carbon-carbon and carbon-hetero atom bonds, catalysed/mediated by copper salts. Though the intermolecular dehydrogenative coupling reactions of copper have already been reviewed more than once, to the best of our knowledge this is the first comprehensive account of copper-based intramolecular dehydrogenative coupling.

Synthesis of functionalized benzo[1,3]dioxin-4-ones from salicylic acid and acetylenic esters and their direct amidation.

Direct synthesis of 4H-benzo[d][1,3]dioxin-4-one derivatives from salicylic acids and acetylenic esters (both mono- and disubstituted) has been described. The reaction is mediated by CuI and NaHCO3 in acetonitrile. Room temperature amidation of the synthesized 1,3-benzodioxinones with primary amines readily afforded the corresponding salicylamides in moderate to good yields.

Aerobic oxidative coupling of arenes and olefins through a biomimetic approach.

Arenes and electron-deficient olefins can be oxidatively coupled through a biomimetic Pd(OAc)2-catalyzed transformation. C-H activation of the arene partner is effected under reaction conditions of low catalyst loading, normal oxygen pressure, and using p-benzoquinone and iron phthalocyanine as electron-transfer mediators (ETMs). By controlling catalyst loading, the reaction can be made selective for either mono- or diarylation.

Biomimetic aerobic oxidation of amino alcohols to lactams.

The right path: N-protected amino alcohols undergo aerobic and biomimetic oxidation to the corresponding lactams in the presence of a ruthenium catalyst and a combination of electron-transfer mediators under air (see scheme). The reaction was used for the synthesis of five-, six-, and seven-, membered lactams and showed good tolerance to a number of N-protecting groups.

NHC-catalysed annulation of enals to tethered dienones: efficient synthesis of bicyclic dienes.

Homoenolates generated from α,ß-unsaturated aldehydes using NHC catalysis underwent facile addition to dibenzylidene cyclohexanone to afford bicyclic cyclopentenes as single diastereomers.

A novel pseudo four component reaction involving homoenolate for the synthesis of gamma-aminobutyric acid (GABA) derivatives.

Homoenolate generated from alpha,beta-unsaturated aldehydes by NHC catalysis underwent facile addition to conjugated sulfonimines, generated in situ, and subsequent methanolysis to afford protected GABA derivatives stereoselectively and in high yields, thus constituting a novel pseudo four component reaction.

Novel nucleophilic heterocyclic carbene mediated stereoselective conjugate addition of enals to nitrostyrenes via homoenolate.

A stereoselective Michael addition of homoenolate, generated from enals by nucleophilic heterocyclic carbene (NHC) catalysis, to beta-nitrostyrenes is reported for the first time. The products of this reaction obtained in good yields are of potential value in the synthesis of a variety of acyclic and heterocyclic compounds.

Nucleophilic heterocyclic carbene catalyzed annulation of enals to chalcones in methanol: a stereoselective synthesis of highly functionalized cyclopentanes.

Homoenolates generated from enals by nucleophilic heterocyclic carbene (NHC) catalysis undergo annulation with chalcones in methanol to afford methyl beta-hydroxycyclopentanecarboxylates, stereoselectively. Construction of four contiguous stereocenters in a stereoselective manner is noteworthy.