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A mild, metal-free,and modular route for the preparation of N-styrenylamidines from N-aryl-α,β-unsaturatednitrones and isocyanates has been developed that accesses an initialoxadiazolidinone intermediate that can undergo CO2eliminationand styrenyl migration. The use of a migration event to install N-styrenyl amidine substituents circumvents a limitationof traditional Pinner-type methods for amidine synthesis that requirethe use of amine nucleophiles. The modularity of the nitrone and isocyanatereagents provides access to a variety of differentially substituted N-styrenyl amidines. The scope and tolerance of the methodare presented, and preliminary mechanistic data for the transformationare discussed. [ABSTRACT FROM AUTHOR]

Palladacycleswere found to be efficient catalysts for the reactionof oxabicyclic alkenes with terminal alkynes. A switch of reactionselectivity was realized using a palladacycle with an sp2or sp3C–Pd bond. Addition products were affordedpredominantly using a palladacycle with an sp3C–Pdbond, while ring-opening compounds were the major products when palladacycleshaving an sp2C–Pd bond were used. DFT calculationsrevealed that the different transeffects of thesp2-C and sp3-C donors in palladacycles areresponsible for the switch in selectivity. [ABSTRACT FROM AUTHOR]

A new synthetic strategy to access polysubstituted furans regiospecifically has been developed using simple bicyclic alkenes and terminal ynones as starting materials with palladacycles as unique active catalysts. A rational mechanism has also been proposed. This reaction features mild reaction conditions, easily available starting materials and palladacycle catalysts, a wide substrate scope, and high regiospecificity. [ABSTRACT FROM AUTHOR]

N-Vinyl nitrones derived from fluorenone have been prepared via a copper-mediated coupling between fluorenone oxime and vinyl boronic acids. These compounds undergo subsequent rearrangement and addition reactions that are distinct from the traditional [3 2] cycloaddition reactivity of nitrones. Thermal rearrangements of fluorenone N-vinyl nitrones give spiroisoxazolines, while treatment with alkynes provides fluorene-tethered isoxazoles. The scope and limitations of the preparation of fluorenone N-vinyl nitrones and their subsequent rearrangement and addition reactions are discussed. [ABSTRACT FROM AUTHOR]

We described an iron(III) and BF 3 ·OEt 2 -promoted oxygen transfer reaction of N -aryl-α,β-unsaturated nitrones to prepare various N , O -difluoroboron β-ketoiminates in good yields ranging from 24% to 87%. Control experiments revealed that the enaminone was the vital intermediate for the formation of N , O -difluoroboron β-ketoiminates, and iron(III) combined with BF 3 ·OEt 2 played as cocatalyst to promote the oxygen transfer reaction through intramolecular cyclization and N-O bond cleavage. More importantly, an estrone-derived N , O -difluoroboron β-ketoiminate was easily prepared in 40% yield from estrone in four steps.

A variety of tetrahydro-5 H -indolo[2,3- b ]quinolines were prepared in 40-97% yields through a copper(II)-catalyzed cascade reaction of aza- o -quinone methides generated in situ from 2-(chloromethyl)anilines and indoles. Experimental results showed that the reaction underwent double 1,4-additions and sequential intramolecular cyclization. The present method features broad substrate scope, good functional group tolerance, and easy gram scalable preparation of indolo[2,3- b ]quinolines.

A type of quinoxaline-derived tridentate N , N , O -ligand was synthesized in good to excellent yields over three steps through iodination of 2-aryl indoles, sequential Kornblum-type oxidation with DMSO, and capture by 1,2-diaminobenzenes. The prepared atropisomeric N , N , O -ligand was successfully applied in the synthesis of N -vinyl cinnamaldehyde nitrones as only Z -isomers in good yields through the Chan-Lam reaction. The method features an easily accessed tunable tridentate N , N , O -ligand, broad substrate scope, good functional group tolerance, and high Z -isomer for N -vinyl nitrones.

We describe a P-containing palladacycle-catalyzed regioselective Heck reaction of 2,3-dihydrofuran with diaryliodonium salts and aryl iodides to afford 2-aryl-2,5-dihydrofurans and 2-aryl-2,3-dihydrofurans, respectively, in good yields. Mechanistic studies revealed that the oxidative addition of diaryliodonium salts to palladacycles to form Pd(IV) species showed high chemoselectivity and that electron-rich aryl moieties were preferentially transferred to the Heck product. DFT calculations indicated that the regioselectivity-determining step is the reductive elimination reaction rather than the isomerization and reinsertion of Pd(IV)-hydride intermediates into the double bond.

A variety of N -vinylindoles and N -vinylpyrroles were prepared in moderate to good yields through the nickel(II)-catalyzed [3 + 2] cycloaddition of α,β-unsaturated nitrones with allenoates under mild reaction conditions. A rational mechanism for the formation of N -vinylindoles was proposed based on the 18 O-labeled experiments and key intermediates detected by high-resolution mass spectrometry trace experiments. The present method highlights a nickel(II)-controlled cyclization, atom-economical reaction, broad substrate scope, good functional group tolerance, and high Z-stereoselectivity for the enamine bond.

Monoamine oxidase A (MAO-A) is a promising diagnostic marker for cancer, depression, Parkinson's disease, and liver disease. The fluorescence detection of MAO-A in living animals is of extreme importance for the early diagnosis of related diseases. However, the development of specific and mitochondrial-targeted and near-infrared (NIR) fluorescence MAO-A probes is still inadequate. Here, we designed and synthesized four NIR fluorescence probes containing a dihydroxanthene (DH) skeleton to detect MAO-A in complex biological systems. The specificity of our representative probe DHMP2 displays a 31-fold fluorescence turn-on in vitro , and it can effectively accumulate in the mitochondria and specifically detect the endogenous MAO-A concentrations in PC-3 and SH-SY5Y cell lines. Furthermore, the probe DHMP2 can be used to visualize the endogenous MAO-A activity in zebrafish and tumor-bearing mice. More importantly, it is the first time that the MAO-A activity of hepatic fibrosis tissues is detected through the probe DHMP2. The present study shows that the synthesized DHMP2 might serve as a potential tool for monitoring MAO-A activity in vivo and diagnosing related diseases.

An approach for the construction of furo[3,2- b ]quinolines and furo[2,3- b :4,5- b' ]diquinolines is developed through a metal-free [4 + 2] cycloaddition of easily available in situ generated aza- o -quinone methides and furans. The reaction tolerates a wide range of aza- o -quinone methides and substituted furans to afford the corresponding dihydro- or tetrahydrofuroquinolines in good to excellent yields. Mechanistic studies reveal that the reaction involves a concerted [4 + 2] cycloaddition pathway and shows a high regioselectivity of cycloaddition for a furan ring. The present method features mild reaction conditions, dearomatization of furans, high regio- and diastereoselectivity, gram-scalable preparations, and diversity of furoquinolines.

In recent years, superhydrophilic and underwater superoleophobic membranes have shown promising results in advanced oil/water separation. However, these membranes still have some drawbacks, like tedious preparation process and instability, which hinder their application in oil/water separation. Accordingly, the development of a facile approach to prepare superhydrophilic membranes with excellent oil/water separation performance is still coveted. Here, a copper mesh decorated with cauliflower-like nickel (Cu mesh@CF-Ni) is synthesized via a facile one-step electrodeposition method. Due to the surface polar -OH and -O-Ni-F groups of the Ni(OH) 2 /NiO x F y shell of the cauliflower-like nickel (CF-Ni), this Cu mesh@CF-Ni displays superhydrophilic and underwater superoleophobic wettability. The results show that the Cu mesh@CF-Ni has excellent oil/water separation efficiency (higher than 99.2%) and ultrahigh water flux (around 20 L h -1 cm -2 ). Moreover, it also displays good stability in a 10 wt % NaCl solution and 1 M NaOH solution for oil/water separation. By introducing the CF-Ni with polar Ni(OH) 2 /NiO x F y components onto the surface of the materials via a simple electrodeposition method, the materials will acquire the capability to not only achieve oil/water separation but also realize many other applications, like self-cleaning, underwater bubble manipulation, and fog harvesting., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

An atom-economical and practical method for the efficient synthesis of various pyrazino[1,2- a ]indole-2-oxides was developed through a nickel(II)-catalyzed [5 + 1] annulation of 2-carbonyl-1-propargylindoles with hydroxylamine in water without using an organic solvent. The reaction involved an initial condensation of 2-carbonyl-1-propargylindoles with hydroxylamine to afford oxime intermediates, which then underwent a nickel(II)-catalyzed 6-exo-dig cyclization. Preliminary studies showed that ( n -Bu) 4 NI served as a phase transfer catalyst and promoted the formation of active nickel(II) species. More importantly, the nickel(II) salt and phase transfer catalyst-in-water could be recycled seven times, and a gram scalable product was easily obtained in good yields through a filtration and washing protocol.

An efficient one-pot synthesis of polysubstituted pyrrolizines from N-vinyl- α,β-unsaturated nitrones and activated alkynes through iron(III)/copper(II)-cocatalyzed [3 + 2] cycloaddition/[3,3]-rearrangement and sequential N-O bond cleavage was developed. The reaction first underwent [3 + 2] cycloaddition and [3,3]-rearrangement to afford nine-membered N-heterocycles, and then a controlled N-O bond cleavage of nine-membered rings by iron(III)/copper(II) cocatalysts delivered pyrrolizine scaffolds. A kinetic resolution of nine-membered ring compounds was achieved for the first time by using copper(II) acetate combined with a chiral PyBox ligand.

A series of 1,2- and 2,3-fused quinazolinones have been synthesized in good to excellent yields through gold-catalyzed selective hydroarylations of alkynyl quinazolinone-tethered pyrroles. The studies revealed that 1,2-fused quinazolinones were obtained through a 1,3-rearrangement and sequential 6- exo-trig cyclization of N1-alkynyl quinazolinone-tethered pyrroles, while N3-alkynyl quinazolinone-tethered pyrroles went through 6- exo-dig or 7- endo-dig cyclizations directly to afford 2,3-fused quinazolinones. The fused quinazolinones could be prepared at gram scale in three steps from commercial ortho-aminobenzamide.

A variety of 2-aminobenzonitriles were prepared from 2-arylindoles in good to excellent yields through tert-butylnitrite (TBN)-mediated nitrosation and sequential iron(III)-catalyzed C-C Bond cleavage in a one-pot fashion. The 2-aminobenzonitriles can be used to rapidly synthesize benzoxazinones by intramolecular condensation. The present method features an inexpensive iron(III) catalyst, gram scalable preparations, and novel C-C bond cleavage of indoles.

An efficient method to synthesize rutaecarpine derivatives via the gold-catalyzed selective cyclization of alkyn-tethered indoles under mild conditions is described. The alkyn-tethered indole can undergo 6-exo-dig cyclization by oxidation and sequential gold catalysis, while it goes through 7-endo-dig cyclization by gold catalysis and sequential oxidation. Substrate scope studies reveal that the selectivity of cyclization was controlled by the substrates with sp 3 and sp 2 hybridization of carbon at the 2 position in quinazolinone. Furthermore, the rutaecarpine scaffold was prepared in 67% yield at gram scale easily in four steps from isatoic anhydride.

p53 inactivation is a clinically defined characteristic for cancer treatment-nonresponsiveness. It is therefore highly desirable to develop anticancer agents by restoring p53 function.1 Herein the synthesized phthalazino[1,2-b]quinazolinones were discovered as p53 activators in bladder cancer cells. 10-Bromo-5-(2-dimethylamino-ethylamino)phthalazino[1,2-b]quinazolin-8-one (5da) was identified as the most promising candidate in view of both its anticancer activity and mechanisms of action. 5da exhibited strong anticancer activity on a broad range of cancer cell lines and significantly reduced tumor growth in xenograft models at doses as low as 6 mg/kg. Furthermore, 5da caused cell cycle arrest at S/G2 phase, induced apoptosis, changed cell size, and led to cell death by increasing the proportion of sub-G1 cells. Molecular mechanism studies suggested that accumulation of phospho-p53 in mitochondria after 5da treatment resulted in conformational activation of Bak, thereby evoking cell apoptosis, finally leading to irreversible cancer cell inhibition. Our present studies furnish new insights into the molecular interactions and anticancer mechanisms of phospho-p53-dependent quinazolinone compound.

A copper-catalyzed selective cross-coupling reaction of 3-(hydroxyimino)indolin-2-ones with alkenyl boronic acids to access (E)-N-vinyl oxindole nitrones has been achieved under mild conditions. The studies showed that catalytic copper salt selectively gave mono N-vinylation products, while 2.0 equiv of copper salt provided double N-vinylation products. The control experiments revealed that the carbonyl group in 3-(hydroxyimino)indolin-2-one played important roles on N-vinylation. Furthermore, the prepared N-vinyl oxindole nitrones could be converted to spirooxindoles in good yields under thermal conditions.

An efficient selective N-arylation of 3-(hydroxyimino)indolin-2-ones with diaryliodonium salts to prepare (Z)-N-aryl oxindole nitrones has been achieved under simple base-mediated conditions. The reaction tolerated a variety of diaryliodonium salts with diverse and sensitive functional groups. Studies on the oxime structures revealed that the pyrroline ring and carbonyl group in 3-(hydroxyimino)indolin-2-ones played important roles in the selective N-arylation process. The N-aryl oxindole nitrones could be prepared rapidly and easily at the gram scale.

A facile synthesis of various spirofluorenylpiperidin-4-ones has been achieved in good yields from fluorenone N-aryl nitrones and methylenecyclopropanes. This method involved an initial cycloaddition to form a 5-spirocyclopropane-isoxazoline, which underwent a highly selective 1,3-rearrangement to give the desired product. The stereochemistry of the spirofluorenylpiperidin-4-one could be controlled by the cycloaddition and sequential rearrangement strategy. Furthermore, the spirofluorenylpiperidin-4-ones could be not only prepared in one-pot procedure but also converted to useful scaffolds by reduction or oxidation conditions.

A metal-free method for synthesis of N-(2-hydroxyaryl)benzotriazoles via O-arylation of N-hydroxybenzotriazoles with readily available diaryliodonium salts and sequential N-O bond cleavage under mild conditions has been developed. The [3,3]-rearrangement of N-O bond cleavage could take place on the N instead of C atom. The reaction was compatible with diverse functional groups and a new type of P,N-ligand was synthesized in three steps.

Metal-free O-arylation and [3, 3]-rearrangement have been shown as an efficient strategy to construct new C-O and C-N bonds in one-pot reactions. The method was used to prepare N-aryl benzo[1,2,3]triazin-4(1H)-one derivatives in good yields from N-hydroxy benzo[1,2,3]triazin-4(3H)-one and diaryliodonium salts. The reaction was tolerated a variety of sensitive functional groups such as iodine, nitro, ester, and aldehyde groups. A rational mechanism was proposed based on the experimental results, and the reaction was easily up to gram scale.

An efficient transition-metal-free method for the preparation of α,β-unsaturated N-aryl ketonitrones under mild conditions has been developed. This reaction shows good functional group tolerance for both electron-rich and electron-deficient substituents on both oximes and diaryliodonium salts. Two examples of gram-scale preparations have been realized in good yields. Further transformations of these nitrones to different N-heterocycles have been demonstrated. DFT calculations suggest that N-arylation products are formed by [1,3]-phenyl migration of an O-coordinated oximate complex via a four-centered transition state, while the O-arylation products are formed by [1,3]-phenyl migration of a N-coordinated oximate complex.

Efficient access to α,α'-diacetoxy ketones has been developed from ethynylcarbinols and PhI(OAc)2. A plausible mechanism for this was proposed on the basis of experimental studies. The usefulness of α,α'-diacetoxy ketone products has been documented, and glycerol derivatives can be easily synthesized in good yields via a one-pot reaction.

An efficient way to access functionalized methylenecyclopropanes has been developed by palladacycle-catalyzed cyclopropanation of bicyclic alkenes with propiolates in high yields. The structure of the palladacycle was kept intact in the reaction, shown by (31)P NMR spectrum studies. A rational mechanism has been proposed with a deuterium-labeled experiment. The usefulness of the functionalized methylenecyclopropanes has also been demonstrated.

Palladacycles showed their high efficiency in the kinetic resolution of 1-hydroxy-2-aryl-1,2-dihydronaphthalenes via dehydration, providing optically active products in high yields and high ee with an S factor up to 26. The superiority of a benzylic-substituted palladacycle in asymmetric induction was also demonstrated.

The chiral phosphine-containing palladacycle, synthesized easily from H-MOP, showed its high catalytic activity as well as asymmetric induction ability in ring-opening reaction of oxabicyclic alkenes with arylboronic acids, providing corresponding products in high yields and high ee.