An Electrochemical Way to Generate Amphiphiles from Hydrazones for the Synthesis of 1,2,4-Triazole Scaffold Cyclic Compounds.

An electro-oxidative cyclization pathway in which hydrazones are selected as starting materials to generate amphiphiles by reacting with benzylamines and benzamides was reported. This strategy successfully prepared a series of 1,2,4-triazoles in satisfactory yields. Moreover, the use of cheap stainless steel as the anode, the feasibility to conduct the transformation as a one-pot reaction and the proof that scaling-up these reactions is possible make this transformation attractive for potential application in industry.

Synthesis of Polysubstituted Pyrroles through Electro-Oxidative Annulation of 1,3-Dicarbonyl Compounds and Primary Amines.

Reported herein is a synthetic method of polysubstituted pyrroles from easily available materials, 1,3-dicarbonyl compounds and primary amines, via electro-oxidative intermolecular annulation. Under similar conditions, enamines are also converted smoothly into desired products, indicating that in situ formed enamines are crucial intermediates for the first transformation. Neither transition-metal salts nor harsh conditions are required to facilitate the dehydrocyclization process.

Discovery of novel 2-aryl-3-sulfonamido-pyridines (HoAns) as microtubule polymerization inhibitors with potent antitumor activities.

Microtubules play a vital role in cell mitosis. Drugs targeting taxol or vinca binding site of tubulin have been proved an effective way to against cancer. However, drug resistance and cancer recurrence are inevitable, there is an urgent need to search for new microtubule-targeting agents (MTAs). In our study, a series of novel 2-aryl-3-sulfonamido-pyridines (HoAns) had been designed, synthesized, and evaluated for their antiproliferative activities in vitro and in vivo. Among them, compound HoAn32 exhibited the most potent activity with IC50 values ranging from 0.170 to 1.193 µM in a panel of cancer cell lines. Mechanism studies indicated that compound HoAn32 bound to the colchicine site of ß-tubulin, resulting in colony formation inhibition, G2/M phase cell cycle arrest, cell apoptosis as well as increased the generation of ROS in both RKO and SW620 cells. In addition, compound HoAn32 showed potent anti-vascular activity in vitro. Furthermore, compound HoAn32 also exhibited outstanding antitumor activity in SW620 xenograft tumor models without observable toxic effects, which was more potent than that of ABT-751. In conclusion, our findings suggest that compound HoAn32 may be a promising microtubule destabilizing agent and deserves for further development in cancer therapy.

Copper/Palladium Bimetallic System for the Synthesis of Isobenzofuranones through [4 + 1] Annulation between Propiophenones and Benzoic Acids.

A copper/palladium-catalyzed annulation from benzoic acids and propiophenones for the synthesis of isobenzofuranones was reported. The Cu-(2,2,6,6-tetramethylpiperidin-1-yl)oxyl system showed a great ability to activate the C-H bond on the α- and ß-carbons of a carbonyl group, and the in situ-generated enone intermediate in this reaction could be further transformed to construct isobenzofuranones with the catalysis of Pd(dba)2 (dba = dibenzylideneacetone). Various isobenzofuranones could be obtained in moderate to good yields, and a great atom economy was highlighted by utilizing this method.

Synthesis of unsymmetrical disulfides via PPh3-mediated reductive coupling of thiophenols with sulfonyl chlorides.

A facile and rapid synthesis of unsymmetrical aryl disulfides using PPh3-mediated reductive coupling of thiophenols with aryl sulfonyl chlorides was described. Good functional group tolerance and scalability were achieved in this strategy. More importantly, the approach enables the introduction of sulfonyl chlorides into the synthesis of asymmetric organic disulfides under catalyst- and base-free conditions. Using this method, unsymmetrical aromatic disulfides could be prepared from inexpensive and readily available starting materials in moderate to excellent isolated yields, through a nucleophilic substitution pathway.

Synthesis of Isoxazolines and Oxazines by Electrochemical Intermolecular [2 + 1 + n] Annulation: Diazo Compounds Act as Radical Acceptors.

Reported herein is an unprecedented synthesis of isoxazolines and oxazines through electrochemical intermolecular annulation of alkenes with tert-butyl nitrite, in which diazo compounds serve as radical acceptors. Notably, [2 + 1 + 2] and [2 + 1 + 3] annulations occur when styrenes and allylbenzenes are used as substrates, respectively. The latter reaction undergoes group migration to form more stable radical, manifesting radical route instead of conventional 1,3-dipolar cycloaddition occurs. Moreover, scale-up experiments suggest the potential application value of these transformations in industry.

Aerobic Copper-Catalyzed Synthesis of (E)-Vinyl Sulfones by Direct C-S Bond Oxidative Coupling.

Copper-catalyzed aerobic oxidative C-S bond coupling reaction between thiophenols and aryl-substituted alkenes for (E)-vinyl sulfones synthesis is reported here. With air utilized as a green oxidant, this transformation not only produces various vinyl sulfones in moderate to good yields but also possesses a simple and ecofriendly system. To clarify the mechanism, kinetic experiments has been investigated.

Iodine-catalyzed synthesis of N,N'-diaryl-o-phenylenediamines from cyclohexanones and anilines using DMSO and O2 as oxidants.

A novel I2-catalyzed cross-dehydrogenative aromatization of cyclohexanones and anilines to synthesize N,N'-diaryl-o-phenylenediamines has been unprecedentedly developed with dimethyl sulfoxide and oxygen employed as mild terminal oxidants. To prove the rationality of the two separate dehydration steps of the proposed mechanism, a resulting I2-catalyzed cross-dehydrogenative aromatization of cyclohexenones and anilines to synthesize diarylamines has also been reported.

Copper(i)-catalyzed N-H olefination of sulfonamides for N-sulfonyl enaminone synthesis.

This communication reports copper-catalyzed N-H olefination of sulfonamides for enaminone synthesis using saturated ketones as olefin sources. With TEMPO derivatives and O2 as oxidants, this method provided an efficient way to produce various enaminones in good yields. Mechanistic studies helped figure out the stable intermediates and develop novel methodologies for the difunctionalization of saturated ketones.

Hemin-catalyzed sulfonium ylide formation and subsequently reactant-controlled chemoselective rearrangements.

Hemin-catalyzed competing routes of [1,2]-Stevens and Sommelet-Hauser rearrangements of benzyl sulfonium ylides through an iron porphyrin carbenoid were established. These rearrangements can be controlled by the electronic property of the substituents on the benzyl group together with solvent effects. Electron-donating or weak electron-withdrawing groups lead to the [1,2]-Stevens rearrangement, whereas strong electron-withdrawing groups at the para-position favor the latter pathway under aqueous conditions.