Palladium-Catalyzed Enantioselective Intramolecular Heck Dearomative Annulation of Indoles with N-Tosylhydrazones.

An elegant Pd(dba)2-catalyzed enantioselective Heck dearomative annulation of indoles and N-tosylhydrazones for the straightforward assembly of structurally diverse optically active indoline scaffolds containing the quaternary carbon centers at the C2 position has been developed. The tandem protocol, which utilized a Pd(dba)2/BINOL-based phosphoramidite ligand as the catalytic system, proceeded smoothly through successive oxidative addition, intramolecular carbon palladation, migratory insertion, and ß-elimination sequences, leading to the chiral indoline derivatives in moderate to excellent yields, with excellent enantioselectivities and diastereoselectivities. In addition, the synthetic practicability of the catalytic system was underlined by a scaled-up experiment and the late-stage derivatization of the products, thus highlighting the potential applications in synthetic chemistry, medicinal chemistry, and material science.

Lewis Acid Catalyzed [4 + 2] Annulation of Propargylic Alcohols with 2-Vinylanilines.

An elegant Lewis acid catalyzed, protection-free, and straightforward synthetic strategy for the assembly of a series of sophisticated polycyclic quinoline skeletons employing propargylic alcohols and 2-vinylanilines as the substrates in the presence of Yb(OTf)3 (10 mol %) and AgOTf (10 mol %) in tetrahydrofuran has been described. This annulation protocol, which proceeds through a sequential Meyer-Schuster rearrangement/nucleophilic substitution/deprotonation sequence, provides a versatile, practical, and atom-economical approach for accessing quinoline derivatives in moderate-to-good yields.

New synthetic approaches toward OCF3-containing compounds.

Fluorinated organic compounds are an important class of organic molecules and play a key role in both academic and industrial communities due to the unique nature of fluorine. Among the fluorine-containing functional groups, the OCF3 group is of vital importance because of its favorable physicochemical properties, so it frequently acts as the pivotal skeletal motif in a broad spectrum of pharmaceutical molecules, agrochemicals, natural products, and materials. Over the past few decades, a wider range of strategies for the efficient, versatile, and practical synthesis of trifluoromethoxylated compounds have been the focus of a number of research initiatives. These synthesis approaches are especially fascinating in the context of the design of agrochemicals and new drugs as established pathways for installing the OCF3 moiety. In this review, the state of the art of the synthesis of OCF3-containing compounds is summarized. It can be segmented into six categories: (1) de novo formation of the OCF3 group; (2) construction of trifluoromethoxylated compounds via trifluoromethylation of the corresponding alcohol or phenol; (3) construction of trifluoromethoxylated compounds via installing the entire OCF3 group straightaway onto a complex molecule; (4) visible-light-induced trifluoromethoxylation; (5) transition metal-catalyzed trifluoromethoxylation; and (6) construction of the trifluoromethoxylated compounds via rearrangement reactions.

Palladium-Catalyzed Intramolecular Heck Dearomative Alkenylation of Indoles with N-Tosylhydrazones.

An elegant Pd-catalyzed intramolecular Heck dearomative alkenylation of aryl iodides with functionalized N-tosylhydrazones proceeded through a sequential dearomative carbopalladation, migratory insertion, and ß-hydride elimination in the presence of Pd(CF3COO)2 (10 mol %), PPh3 (30 mol %), and Cs2CO3 (2.0 equiv) in 1,4-dioxane (2.0 mL) at 120 °C for 14 h under an argon atmosphere. This cascade cycloaddition protocol provided a reliable and versatile approach to a sequence of structurally diverse indolines in moderate to good yields with good functional group compatibility. In addition, the synthetic robustness of the methodology is highlighted by a scaled-up experiment and derivatization of products via epoxidation and reduction reactions.

Visible-Light-Induced Oxyalkylation of 1,2,4-Triazine-3,5(2H, 4H)-diones with Ethers via Oxidative Cross-Dehydrogenative Coupling.

An efficient and convenient method to synthesize 6-oxyalkylated 1,2,4-triazine-3,5(2H, 4H)-diones has been developed via visible-light-induced cross-dehydrogenative coupling reaction between 1,2,4-triazine-3,5(2H, 4H)-diones and ethers with a wide range of functional group tolerance. The present transformation employs the cheap and low-toxic 2-tert-butylanthraquinone as a metal-free photocatalyst and air as a green oxidant at room temperature. Moreover, this reaction can also be driven by sunlight as a clean energy resource. The synthetic utility of this method is further demonstrated by gram-scale reaction and application in the preparation of key intermediates of bioactive molecules.

Primary Amination of Ar2P(O)-H with (NH4)2CO3 as an Ammonia Source under Simple and Mild Conditions and Its Extension to the Construction of Various P-N or P-O Bonds.

A facile and efficient method for the synthesis of primary phosphinamides from Ar2P(O)-H reagents with stable and readily available ammonium carbonate as an ammonia source is disclosed herein for the first time. This ethyl bromoacetate-mediated primary amination proceeds smoothly under mild and simple conditions, without any metal catalyst or oxidant. Moreover, this method is also appropriate for the reaction of Ar2P(O)-H with a variety of amines, alcohols, and phenols to construct P-N or P-O bonds, with features of handy operation, good functional group tolerance, and broad substrate scope.

Palladium-Catalyzed Asymmetric Intramolecular Dearomative Heck Annulation of Aryl Halides to Furnish Indolines.

An unprecedented Pd-catalyzed asymmetric intramolecular cascade cyclization of aryl halides with readily available arylboronic acids proceeds through a Heck-type dearomative cyclization terminated with arylation in the presence of Pd2(dba)3 (10 mol %), Cu2O (5 mol %), and Cs2CO3 (2.0 equiv) in 1,2-dichloroethane (1.0 mL) at 100 °C for 15 h in air using BINOL-based phosphoramidite as the chiral ligand. This dearomative Heck protocol, which tolerates a broad variety of functional groups, is amenable to the generation of optically active indoline derivatives bearing all-carbon quaternary stereogenic centers in one step in moderate to excellent yields, with excellent diastereoselectivities (>20:1) and enantioselectivities (up to >99% ee). It is worth mentioning that no decrease in the enantiopurity of the indoline derivatives was observed during the synthetic transformations of the products.

Visible-Light-Induced C(sp2)-C(sp3) Cross-Dehydrogenative-Coupling Reaction of N-Heterocycles with N-Alkyl-N-methylanilines under Mild Conditions.

Disclosed herein is a cross-dehydrogenative-coupling reaction of N-heterocycles including 1,2,4-triazine-3,5(2H, 4H)-diones and quinoxaline-2(1H)-ones with N-methylanilines to form C(sp2)-C(sp3) under visible-light illumination and ambient air at room temperature. In this process, easily available Ru(bpy)3Cl2·6H2O serves as the catalyst, and air acts as the green oxidant. This method features high atom economy, environmental friendliness, and convenient operation and provides an efficient and practical access to aminomethyl-substituted N-heterocycles with extensive functional group compatibility in 40-86% yields.

Direct Introduction of Sulfonamide Groups into Quinoxalin-2(1H)-ones by Cu-Catalyzed C3-H Functionalization.

Direct sulfonamidation of quinoxalin-2(1H)-one derivatives has been developed using a readily available Cu salt as the catalyst and inexpensive ammonium persulfate as the oxidant in moderate conditions. Owing to the feature of handy operation and good functional group tolerance, this method provides a convenient and efficient access to curative 3-sulfonamidated quinoxalin-2(1H)-one scaffolds.

Synthesis of 1,6-Dihydropyridine-3-carbonitrile Derivatives via Lewis Acid-Catalyzed Annulation of Propargylic Alcohols with (E)-3-Amino-3-phenylacrylonitriles.

A novel Lewis acid-catalyzed, highly efficient, practical, and atom-economical protocol for the synthesis of functionalized 1,2-dihydropyridine-3-carbonitrile derivatives in the presence of Bi(OTf)3 (10 mol %) in tetrahydrofuran (2.0 mL) at 80 °C for 8 h in air is described, starting from readily accessed propargylic alcohols and (E)-3-amino-3-phenylacrylonitriles. This cycloaddition protocol, which is scalable and proceeds under mild conditions, is amenable to the gram-scale construction of valuable 1,2-dihydropyridine-3-carbonitriles. Furthermore, the good functional group compatibility and broad scope of this strategy were demonstrated by a broad range of propargylic alcohols and (E)-3-amino-3-phenylacrylonitriles, with yields ranging from 34 to 96%.

Silver Trifluoromethanesulfonate-Catalyzed Annulation of Propargylic Alcohols with 3-Methyleneisoindolin-1-one.

A silver-catalyzed formal [3 + 3] annulation of 3-methyleneisoindolin-1-one with alkynol for the synthesis of 1,5-dihydroindolizin-3(2H)-one derivatives is disclosed. The protocol allows practical synthesis of N-heterocyclic scaffolds with a broad scope of functional groups and could be efficiently scaled up to gram scale, which incarnates a potential application of this methodology. In addition, a range of chlorine anion substitution of alkenes can be constructed by adjusting the structure of the alkynol substrates with the use of TMSCl.

Meteorological factors and water quality changes of Plateau Lake Dianchi in China (1990-2015) and their joint influences on cyanobacterial blooms.

Cyanobacterial blooms (CBs) in eutrophic lakes can cause various harmful issues to both humans and animals, disturb drinking water supply, and devastate lake ecosystems. Although great progresses have been made in many lakes from China and abroad on CBs prevention, mitigation and control, systematic research on the influencing factors of CBs in hypereutrophic plateau Lake Dianchi over a long time span is so far unavailable. This study comprehensively generalized both meteorological and water quality changes in Lake Dianchi during 1990-2015 on both yearly and monthly basis, separated Caohai from Waihai of Lake Dianchi regarding water quality variations, and investigated the individual and joint influencing meteorological and water quality factors on CBs using Spearman correlation, principal component analysis, and multivariate linear stepwise regression. Four specific lake regions, i.e. Caohai, northern Waihai, central Waihai, and southern Waihai, were respectively analyzed due to significant water quality heterogeneity. Results indicated that mild temperatures, low wind velocities, and hypereutrophic water conditions all favor CBs in Lake Dianchi, and the significant temperature rising trend may exacerbate severer CBs in the future. Despite configuration differences, the first principal components on CBs in the four sub-regions of Lake Dianchi were all consisted of meteorological factors, while water quality parameters especially total phosphorus concentrations contributed to the second principal component. Quantification of joint meteorological and water quality influencing factors on CBs needs further improvement, and largely relies on the accuracy of future weather forecasts, in order to set the goal of water quality improvement in each specific lake region for effective CBs management.

Base promoted direct difunctionalization/cascade cyclization of 1,6-enynes.

A novel base-mediated direct difluoroalkylation of 1,6-enynes involving a CF2 radical process has been developed. In the absence of metal catalysts, two different difluoroalkylated cyclization products have been synthesized with good functional group applicability and high stereoselectivity. Notably, the properties of a base have been shown to play a crucial role in the generation selectivity of this transformation.

Synthesis of Organophosphorus Compounds through Copper-Catalyzed Annulation Involving C-O and C-P Bond Formations.

A novel copper(II) trifluoromethanesulfonate-catalyzed, high-efficiency, and atom-economical synthesis of valuable organophosphorus compounds via cascade annulation of propargylic alcohols with diphenylphosphine oxide is described. This protocol, which has a good functional-group compatibility and insensitivity to an ambient atmosphere, provides a simple and direct pathway to the products, organophosphorus compounds, in good yields under mild conditions. The method could be efficiently scaled up to gram scale, thus highlighting a potential application of this methodology.

Copper-Catalyzed Oxidative Cyclization of Alkynes with Sulfonylhydrazides Leading to 2-Sulfonated 9H-pyrrolo[1,2-a]indol-9-ones.

A copper-catalyzed oxidative cyclization procedure has been developed for the production of 2-sulfonated 9H-pyrrolo[1,2-a]indol-9-ones via the direct sulfonylation of N-propargyl-substituted indoles with sulfonylhydrazides and tert-butyl hydroperoxide (TBHP). This novel protocol, which tolerates a broad range of functional groups, offers a simple, efficient, and atom-economical route to a series of fluorazones in good yields under mild conditions.

Lewis Acid Catalyzed Dehydrogenative Coupling of Tertiary Propargylic Alcohols with Quinoline N-Oxides.

An unprecedented Lewis acid catalyzed, high-efficiency synthesis of valuable 2-(quinolin-2-yl)prop-2-en-1-ones via dehydrogenative coupling of propargylic alkynols with quinoline N-oxides is described. This protocol, which tolerates a broad range of functional groups, provides a straightforward pathway to the products 2-(quinolin-2-yl)prop-2-en-1-one scaffolds in satisfactory yields. The conversion could be scaled up to gram scale efficiently, which underlines a latent application of this methodology.

[Comparison of Ex Vivo Expanded and Highly Purified NK Cell-Mediated Cytotoxicity Detected by 3 Different Staining Methods of Flow Cytometry].

OBJECTIVE: To compare the cytotoxicity of ex vivo expanded NK cells detected by flow cytometry with 3 different staining methods. METHODS: NK cells were collected from peripheral blood on the 17th day after culture. The cultured cells were divided into 3 groups: group A , B, and C. The cells in group A were stained with CFSE/Annectin-V/7-AAD; the cells in group B were stained with Annectin-V/PI, and the cells in group C cells were stained with CFSE/PI. The E:T ratios in 3 groups were 10:1, 20:1 and 40:1, respectively, the K562 cells were incubated with NK cells for 4 hrs. RESULTS: The purity of NK cells(CD3-CD56+) reached to (16.34±10.51)% on day 0 and to (83.63±10.63)% on the day 17 after incubation(P<0.05); the cytotoxicity of group A was significantly higher than thay of group B at different E:T ratio (P<0.05). The cytotoxicities in A, B, C groups at E:T ratio=10:1 were (36.56±3.69)%, (10.85±2.09)% and (22.35±2.71)% respectively; the cytotoxicities in A, B, C groups at E:T ratio=9:1 were (47.83±5.52)%, (39.07±5.55)% and (29.61±4.81)%; the cytotoxicities in A, B, C groups at E:T ratio=40:1 were (67.7±4.77)%, (51.51±4.43)% and (44.12±5.62)% respectively. Meanwhile, the cytotoxicity in group A was significantly higher than that in group C at different E:T ratio (P<0.05), the percentage of cytotoxicity was (36.56±3.69)% vs (10.85±2.09)%, (47.83±5.52)% vs (29.61±4.81)%, (67.7±4.77)% vs (44.12±5.62)%, respectively. CONCLUSION: CFSE/Annectin-V/7-AAD is able to clearly show human NK cell cytotoxicity against human tumors. Moreover, this staining technique also allows to distinguish different stages of cytotoxic killing as early and late apoptotic phase.

Merging photoredox with copper catalysis: decarboxylative difluoroacetylation of α,ß-unsaturated carboxylic acids with ICF2CO2Et.

A photoredox-/copper-catalyzed decarboxylative difluoroacetylation reaction of α,ß-unsaturated carboxylic acids has been developed. This reaction produces a variety of difluoroalkylated alkenes in moderate to excellent yields and exhibits satisfactory stereoselectivity and a broad substrate scope at ambient temperature. Furthermore, this decarboxylative difluoroacetylation protocol provides efficient and environment friendly access to the difluoroalkylated alkenes.

Lewis Acid Catalyzed Cyclization of Propargylic Alcohols with 2-Vinylphenol.

An unprecedented Lewis acid catalyzed, protection-free, and high-efficiency synthesis of valuable 3,4-dihydro-2H-2,4-methanochromans via cycloaddition of propargylic alkynols with 2-vinylphenol is described. This cycloaddition protocol, which tolerates a wide variety of functional groups, provides practical, versatile, and atom-economical access to a new class of appealing bridged-ring products in satisfactory yields. Compared with the reported reaction conditions for bridged-ring skeletons synthesis, the present reaction conditions are neutral, mild, and without any additives.

BF3·OEt2-AgSCF3 Mediated Trifluoromethylthiolation/Cascade Cyclization of Propynols: Synthesis of 4-((Trifluoromethyl)thio)-2H-chromene and 4-((Trifluoromethyl)thio)-1,2-dihydroquinoline Derivatives.

A BF3·OEt2-AgSCF3 mediated direct trifluoromethylthiolation/cascade cyclization of propynols involving the SCF3 anion nucleophilic pathway is developed. This protocol also provides an opportunity to construct valuable trifluoromethylthio-substituted 2H-chromene and 1,2-dihydroquinoline systems with high efficiency under mild conditions. Additionally, the developed BF3·OEt2-AgSCF3 reaction system could be scaled up to gram quantities in a satisfactory yield without inert gas protection.