Oxidative alkylation/alkynylation of terminal alkenes via alkylaldehyde decarbonylation and 1,2-alkynyl migration.

A metal-free oxidative alkene alkylation/alkynylation of 1,4-enyn-3-ols with alkylaldehydes has been achieved, which offers a general access to the challenging quaternary carbon-containing but-3-yn-1-ones. The method features excellent functional group tolerance, broad substrate scope and exquisite selectivity, and provides a strategy for the difunctionalization of functional alkenes and utilization of alkylaldehydes as alkylating reagents through decarbonylation and 1,2-alkynyl migration.

One-Pot Three-Component Synthesis of Novel Diethyl((2-oxo-1,2-dihydroquinolin-3-yl)(arylamino)methyl)phosphonate as Potential Anticancer Agents.

With the aim of discovering new anticancer agents, we have designed and synthesized novel α-aminophosphonate derivatives containing a 2-oxoquinoline structure using a convenient one-pot three-component method. The newly synthesized compounds were evaluated for antitumor activities against the A549 (human lung adenocarcinoma cell), HeLa (human cervical carcinoma cell), MCF-7 (human breast cancer cell), and U2OS (human osteosarcoma cell) cancer cell lines in vitro, employing a standard 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The results of pharmacological screening indicated that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most compounds showed more potent inhibitory activities comparable to 5-fluorouracil (5-FU) which was used as a positive control. The mechanism of representative compound 4u (diethyl((2-oxo-1,2-dihydroquinolin-3-yl)(phenyl-amino)methyl)phosphonate) indicated that the compound mainly arrested HeLa cells in S and G2 stages and was accompanied by apoptosis in HeLa cells. This action was confirmed by acridine orange/ethidium bromide staining, Hoechst 33342 staining, and flow cytometry.

Synthesis of benzocyclohepta[b]indoles by Lewis acid catalyzed annulation of two 3-(1H-isochromen-1-yl)-1H-indoles.

A novel Lewis acid catalyzed annulation reaction has been established for the synthesis of benzocyclohepta[b]indoles. This method represents a new annulation strategy to a seven-membered carbocyclic ring system from two 3-(1H-isochromen-1-yl)-1H-indole molecules using Cu(OTf)2 catalyst; moreover, the products, benzocyclohepta[b]indoles, can be used as the rapid mercuric ion colorimetric detection reagents.

Palladium-catalyzed synthesis of 3-acylated indoles involving oxidative cross-coupling of indoles with α-amino carbonyl compounds.

A new and selective C-N bond oxidative cleavage method to 3-acylated indoles by Pd-catalyzed oxidative cross coupling of indoles with α-amino carbonyl compounds has been developed; moreover, one-pot synthesis of 3-acylated indoles from 2-ethynylanilines and α-amino carbonyl compounds has also been established. Importantly, the products 3-acylated indoles can be used to construct polyheterocyclic compound, which can be employed as efficient probes for Hg(2+) and Fe(3+).

Determination of trace amount of Cu2+ with a multi-responsive colorimetric and reversible chemosensor.

A multi-responsive sensor 1 was constructed by combining a ferrocene unit and a rhodamine block via a carbohydrazone bond. The sensor showed high selectivity toward Cu(2+) over other common metal ions in a wide pH range with excellent reversibility and rapid response. The obvious color change from colorless to pink upon the addition of Cu(2+) could make it a suitable 'naked-eye' indicator for Cu(2+). The detection limit (LOD) obtained was down to 2.0 nM and the association constant (Ka) was evaluated as 4.65 × 10(7) M(-1). The accuracy for detecting Cu(2+) in environmental river water was compared favorably with the traditional atomic absorption spectroscopy method (AAS). Finally, we proposed a reversible ring-opening mechanism (Off-On) of the rhodamine spirolactam induced by Cu(2+) binding and a 2 : 1 stoichiometric structure between 1 and Cu(2+).

Merging Photoredox/Nickel Catalysis for Cross-Electrophile Coupling of Aziridines with Pyridin-1-ium Salts via Dearomatization.

Merging photoredox/nickel catalysis enabling the cross-electrophile coupling of aziridines with pyridin-1-ium salts involving dearomatization for the synthesis of ß-(1,4-dihydropyridin-4-yl)-ethylamines, especially including bioactive motif-based analogues, is described. This method allows incorporation of a 1,4-dihydropyridin-4-yl group and formation a N-H amino group to construct highly valuable ß-(1,4-dihydropyridin-4-yl)-ethylamine frameworks in a single step through the C2-N bond regioselective cleavage and dearomatization alkylation cascades with precise regioselectivity and excellent functional group tolerance, and represents an appealing cross-electrophile coupling strategy to accomplish transformations between two electrophiles, including aziridines and pyridin-1-ium salts, by avoiding prefunctionalization.

Nickel-Catalyzed Arylcarbamoylation of Alkenes of N-(o-Iodoaryl)acrylamides with Nitroarenes via Reductive Aminocarbonylation: Facile Synthesis of Carbamoyl-Substituted Oxindoles.

Nickel-catalyzed arylcarbamoylation reactions of alkenes of N-(o-haloaryl)acrylamides with CO and nitroarenes via reductive aminocarbonylation to produce carbamoyl-substituted oxindoles with an all-carbon quaternary stereogenic center are presented. Starting with N-(o-haloaryl)acrylamides, simple CO, and inexpensive nitroarenes and using a Ni catalyst, a dinitrogen-based ligand, a Zn reductant, a TMSCl additive, and a base system, this protocol enables the synthesis of various carbamoyl-substituted oxindoles and allows the efficient late-stage derivatization of valuable molecules.

One-Carbon Incorporation Using Cyclobutanone Oxime Ester Enabled [2 + 2 + 1] Carboannulation of 1,7-Enynes by C-C/N-O Bond Cleavage and C-H Functionalization.

A NiCl2-promoted [2 + 2 + 1] carboannulation of 1,7-enynes with internally oxidative cyclobutanone oximes to produce canyo-functionalized 4H-cyclopenta[c]quinolin-4-ones is disclosed. Through C-C/N-O bond cleavage and C-H functionalization, the process enables one-carbon incorporation using cyclobutanone oximes to achieve [2 + 2 + 1] carboannulation of 1,7-enynes, which is highlighted by allowing the formation of four new bonds with high selectivity and broad substrate scope.

Metal-free oxidative [2+2+1] heteroannulation of 1,7-enynes with thiocyanates toward thieno[3,4-c]quinolin-4(5H)-ones.

A new metal-free oxidative [2+2+1] heteroannulation of 1,7-enynes with thiocyanates for producing thieno[3,4-c]quinolin-4(5H)-ones is presented. This reaction employs benzoylperoxide (BPO) as the oxidant and sodium thiocyanate as the sulfur source to enable the formation of three chemical bonds, two C-S bonds and one C-C bond, in a single reaction, and represents a new, practical access to S-heterocycles with the avoidance of the use of metal catalysts and excess bases.

Copper-Catalyzed C-H Oxidative Radical Functionalization and Annulation of Aniline-Linked 1,7-Enynes: Evidence for a 1,5-Hydride Shift Mechanism.

A new copper-catalyzed tandem C-H oxidative radical functionalization and annulation of aniline-linked 1,7-enynes with alkyl nitriles or acetone is described. This reaction allows the selective construction of 1H-cyclopenta[c]quinolines and benzo[j]phenanthridin-6(5H)-ones which rely on the substitution effect at the 2-position of the acrylamide moiety. The mechanism involving a 1,5-hydride shift process is proposed according to the control deuterium-labeled experiment.

Cleaved DNAzyme substrate induced enzymatic cascade for the exponential amplified analysis of L-histidine.

A novel strategy of cleaved DNAzyme substrate induced enzymatic cascade has been devised for the exponential amplified detection of L-histidine. The enzyme strand carries out hydrolytic cleavage of the substrate strand in the presence of L-histidine. The cleaved DNAzyme substrates introduce the polymerase/endonuclease reaction cycles as primers. The L-histidine acts as the activator for enzymatic cascade amplification generating a distinguishable fluorescence enhancement. A good nonlinear correlation (R=0.9994) between fluorescence intensity and the logarithm of the L-histidine concentration is obtained over the range from 50 nM to 1.0 mM. The detection limit was estimated as 30 nM. This efficient amplification of the fluorescence signal is attributed to the L-histidine induced cooperation of Klenow Fragment polymerase (exo(-)) and Nb.BbvCI endonuclease reaction. The activation of such enzymatic cascades through analyte-DNAzyme interactions has a substantial impact on the development of exponential amplified DNAzyme sensors.

Palladium-catalyzed thiolation of alkanes and ethers with arylsulfonyl hydrazides.

A new method for the preparation of alkyl aryl sulfides through direct oxidative thiolation of alkanes or ethers with arylsulfonyl hydrazides using di-tert-butyl peroxide (DTBP) as an oxidant catalyzed by Pd(OAc)2 has been reported. The C-H bonds in various alkanes or ethers were successfully converted into C-S bonds to yield the corresponding sulfides in moderate to good yields.

Metal-free oxidative C(sp3)-H bond thiolation of ethers with disulfides.

A novel method for the preparation of alkyl aryl sulfides through direct oxidation thiolation of commercial ethers with diaryl disulfides using di-tert-butyl peroxide (DTBP) as the oxidant without a metal catalyst was established. The C(sp(3))-H bond in various ethers was successfully converted into a C-S bond, and the corresponding sulfides were achieved with moderate to high yields.

TBHP-mediated oxidative thiolation of an sp3 C-H bond adjacent to a nitrogen atom in an amide.

The first example of molecular sieve-promoted TBHP-mediated direct oxidative thiolation of an sp(3) C-H bond adjacent to a nitrogen atom with disulfides under metal-free conditions, which allows for preparation of numerous S,N-containing compounds, is presented. Moreover, diverse benzothiazoles and a fipronil analog can be synthesized through this strategy.

A novel fluorescent probe for copper ions based on polymer-modified CdSe/CdS core/shell quantum dots.

Quantum dots (QDs) have become one of the most attractive fields of current research because of their unique optical properties. Novel copper-sensitive fluorescent fluoroionophores based on CdSe/CdS core/shell QDs modified with a polymer of MAO-mPEG were synthesized and characterized in the present work. A pH of 6.47 was optimally selected for measurements. By modifying QDs with MAO-mPEG, significant aqueous fluorescence quenching was observed upon binding with copper ions involving both reduced and oxidized environments, indicating great sensitivity and specificity for copper-ion sensing. No significant interfering effects from other metal ions, such as Ag(+), Al(3+), Ba(2+), Ca(2+), Cd(2+), Co(2+), Cr(3+), Fe(2+), Fe(3+), Hg(2+), K(+), Mg(2+), Mn(2+), Na(+), Ni(2+), Pb(2+), Sn(2+), and Zn(2+), were observed. The linear response range for Cu(2+) was found to be 0.01-0.50 µM, and the limit of detection was evaluated to be 16 nM. The proposed method demonstrated improved sensitivity and selectivity characteristics for Cu(II) determinations based on CdSe/CdS core/shell QDs modified with MAO-mPEG by using a typical liquid-phase quenching assay, showing its potential application to multiplex sensing of different analytes through distinct ligand conjugation and functionalization of individual fluorophores.

A stilbene-based fluoroionophore for copper ion sensing in both reduced and oxidized environments.

The high sensitivity and abundance of fluorophores makes fluorescence technique among one of the most promising tools to develop chemo- and biosensors. Fluorescent sensors for ions, also called fluoroionophores, are commonly composed of an ion recognition unit (ionophore) and a fluorogenic unit (fluorophore). Here we report the synthesis and characterization of a new stilbene derivative conjugated with the di-2-picolylamine (dpa) group. It is found that the fluorescence of the stilbene derivative using dpa as ionophore is sensitive to copper ions, including Cu(2+) (oxidized state) and Cu(+) (reduced state). The sensitive and selective stilbene-based fluoroionophore for copper ions are based on the internal charge transfer along with the electron donor-pi-acceptor stilbene motif and incorporate a dpa-containing aniline-derivatized ligand framework. By modifying the stilbene with di-2-picolylamine (dpa), the significant fluorescence quenching was observed upon binding with copper ions involving both the reduced and oxidized environments, indicating the great sensitivity and specificity for copper ion sensing. The presence of metal ions such as Ag(+), Al(3+), Ba(2+), Ca(2+), Cd(2+), Co(2+), Cr(3+), Fe(2+), Fe(3+), Hg(2+), K(+), Mg(2+), Mn(2+), Na(+), Ni(2+), Pb(2+), Sn(2+), and Zn(2+) had little influence on the selectivity and sensitivity of Cu(2+) and Cu(+). The optical sensor design undertakes promising for potential application to multiplex sensing of different analytes through distinct ligand conjugation and functionalization of individual fluorophore.