Cyclization Reactions of In Situ-Generated Acyl Ketene with Ynones to Form Oxacycles.

Acyl ketenes react with polar unsaturated functional groups to give unique heterocyclic rings, yet reactions with unpolarized unsaturated functional groups have not been reported. Herein, we describe two effective ring-forming reactions between acetyl ketene and electron-deficient alkynes. The first reaction involves in situ tethering between acetyl ketene and nucleophile-containing 1,3-diynones, which promotes sequential intramolecular 1,6/1,4-additions to generate 2-methylene-2H-pyrans in various yields (24-91%). The other involves a zwitterionic intermediate generated from acetyl ketene and DABCO, which undergoes a Michael addition with terminal alkynyl ketones to generate 3-acyl-4-pyrones (11-79%).

Cycloisomerization of Alkyne-Tethered N-Acyloxycarbamates to 2-(3H)Oxazolones through Nitrenoid-Mediated Carboxyamidation.

The cycloisomerization of alkyne-tethered N-benzoyloxycarbamates to 2-(3H)oxazolones is described. Two catalytic systems are tailored for intramolecular 5-exo-alkyne carboxyamidation and concomitant alkene isomerization. PtCl2 /CO (5 mol%, toluene, 100 °C) promotes both carboxyamidation and alkene isomerization but has a limited substrate scope. On the other hand, FeCl3 (5 mol%, CH3 CN, 100 °C) promotes carboxyamidation effectively but a cocatalyst is required for the exocyclic alkene isomerization. Thus, a two-step one-pot protocol has been developed for a broader reaction scope, which involves FeCl3 -catalyzed carboxyamidation and base-induced alkene isomerization. Crossover experiments suggest that these reactions proceed mainly through a mechanism involving acylnitrenoid intermediates rather than carbenoid intermediates.

Visible-Light-Promoted Hydrogenation of Azobenzenes to Hydrazobenzenes with Thioacetic Acid as the Reductant.

A catalyst- and metal-free hydrogenation of azobenzenes to hydrazobenzenes in the presence of thioacetic acid was achieved under visible light irradiation. The transformation was carried out under mild conditions in an air atmosphere at ambient temperature, generating a variety of hydrazobenzenes with yields up to 99%. The current process is compatible with a variety of substituents and is highly chemoselective for azo reduction when other unsaturated functionalities (carbonyl, alkenyl, alkynyl, etc.) are contained. Preliminary mechanistic study indicated that the transformation could be a radical process.

Study on the Dynamic Changes in Non-Volatile Metabolites of Rizhao Green Tea Based on Metabolomics.

The processing of tea leaves plays a crucial role in the formation of the taste of the resulting tea. In order to study the compositions of and changes in taste-related substances during the processing of Rizhao green tea, non-targeted metabolomics was used, based on UHPLC-Q Exactive MS. Totals of 529, 349, and 206 non-volatile metabolites were identified using three different detection modes, of which 112 secondary metabolites were significantly changed. Significant variations in secondary metabolites were observed during processing, especially during the drying stage, and the conversion intensity levels of non-volatile metabolites were consistent with the law of "Drying > Fixation > Rolling". The DOT method was used to screen tea-quality-related compounds that contributed significantly to the taste of Rizhao green tea, including (-)-epicatechin gallate, (-)-epicatechin gallate, gallic acid, L-theanine, and L-leucine, which make important contributions to taste profiles, such as umami and bitterness. Metabolic pathway analysis revealed that purine metabolism, caffeine metabolism, and tyrosine metabolism perform key roles in the processing of Rizhao green tea in different processing stages. The results of this study provide a theoretical basis for tea processing and practical advice for the food industry.

Development of an Allenyne-Alkyne [4+2] Cycloaddition and its Application to Total Synthesis of Selaginpulvilin A.

A new [4+2] cycloaddition of allenyne-alkyne is developed. The reaction is believed to proceed with forming an α,3-dehydrotoluene intermediate. This species behaves as a σπ-diradical to react with a hydrogen atom donor, whereas it displays a zwitterionic reactivity toward weak nucleophiles. The efficiency of trapping α,3-dehydrotoluene depends not only on its substituents but also the trapping agents. Notable features of the reaction are the activating role of the extra alkyne of the 1,3-diyne that reacts with the allenyne moiety and the opposite mode of trapping with oxygen and nitrogen nucleophiles. Oxygen nucleophiles result in the oxygen-end incorporation at the benzylic position of the α,3-dehydrotoluene, whereas with amine nucleophiles the nitrogen-end is incorporated into the aromatic core. Relying on the allenyne-alkyne cycloaddition as an enabling strategy, a concise total synthesis of phosphodiesterase-4 inhibitory selaginpulvilin A is realized.

Cobalt-Catalyzed Z to E Geometrical Isomerization of 1,3-Dienes.

An efficient cobalt-catalyzed geometrical isomerization of 1,3-dienes is described. In the combination of a CoCl2 precatalyst with an amido-diphosphine-oxazoline ligand, the geometrical isomerization of E/Z mixtures of 1,3-dienes proceed in a stereoconvergent manner, affording (E) isomers in high stereoselectivity. This facile transformation features a broad substrate scope with good functional group tolerance and could be scaled up to the gram scale smoothly with a catalyst loading of 1 mol %.

Amide/Ester Cross-Coupling via C-N/C-H Bond Cleavage: Synthesis of ß-Ketoesters.

Activated primary, secondary, and tertiary amides were coupled with enolizable esters in the presence of LiHMDS to obtain good yields of ß-ketoesters at room temperature. Notably, this protocol provides an efficient, mild, and high chemoselectivity method to synthesis of ß-alkylketoesters using the cross-coupling between aliphatic amides and esters. Meanwhile, gram-scale secondary and primary amides reacted via in situ generated activated tertiary amides and exhibited good reactivity when coupled with esters.

A Unified Catalytic Asymmetric (4+1) and (5+1) Annulation Strategy to Access Chiral Spirooxindole-Fused Oxacycles.

A unified catalytic asymmetric (N+1) (N=4, 5) annulation reaction of oxindoles with bifunctional peroxides has been achieved in the presence of a chiral phase-transfer catalyst (PTC). This general strategy utilizes peroxides as unique bielectrophilic four- or five-atom synthons to participate in the C-C and the subsequent umpolung C-O bond-forming reactions with one-carbon unit nucleophiles, thus providing a distinct method to access the valuable chiral spirooxindole-tetrahydrofurans and -tetrahydropyrans with good yields and high enantioselectivities under mild conditions. DFT calculations were performed to rationalize the origin of high enantioselectivity. The gram-scale syntheses and synthetic utility of the resultant products were also demonstrated.

Pd-Catalyzed Decarboxylative Olefination: Stereoselective Synthesis of Polysubstituted Butadienes and Macrocyclic P-glycoprotein Inhibitors.

The efficient and stereoselective synthesis of polysubstituted butadienes, especially the multifunctional butadienes, represents a great challenge in organic synthesis. Herein, we wish to report a distinctive Pd(0) carbene-initiated decarboxylative olefination approach that enables the direct coupling of diazo esters with vinylethylene carbonates (VECs), vinyl oxazolidinones, or vinyl benzoxazinones to afford alcohol-, amine-, or aniline-containing 1,3-dienes in moderate to high yields and with excellent stereoselectivity. This protocol features operational simplicity, mild reaction conditions, a broad substrate scope, and gram-scalability. Notably, a structurally unique allylic Pd(II) intermediate was isolated and characterized. DFT calculation and control experiments demonstrated that a rare Pd(0) carbene intermediate could be involved in this reaction. Moreover, the polysubstituted butadienes as novel building blocks were unprecedentedly assembled into macrocycles, which efficiently inhibited the P-glycoprotein and dramatically reversed multidrug resistance in cancer cells by 190-fold.

Synthesis of Titanium Complexes Supported by Carbinolamide- and Amide-Containing Ligands Derived from Ti(NMe2)4-Mediated Selective Amidations of Carbonyl Groups.

An efficient strategy for the syntheses of a series of titanium complexes has been developed. This protocol features the employment of Ti(NMe2)4 both as the metal center to trigger the deprotonation of the ligands and as an amine source to proceed the amidation reactions of carbonyl functionalities of the ligands. Treatment of Ti(NMe2)4 with a ligand HL1 (HL1 = 2,2'-(((2-hydroxybenzyl)azanediyl)bis(ethane-2,1-diyl))bis(isoindoline-1,3-dione) results in the formation of Ti(L1')(NMe2) (1) (H3L1' = N1-(2-((2-(1-(dimethylamino)-1-hydroxy-3-oxoisoindolin-2-yl)ethyl)(2-hydroxybenzyl)amino)ethyl)-N2,N2-dimethylphthalamide). One important feature regarding the synthesis of 1 is the occurrence of the in situ metal-ligand reaction between Ti(NMe2)4 and HL1, leading to the simultaneous formations of carbinolamide and amide scaffolds. Another prominent feature in terms of the preparation of 1 is the achievement of the selective ring-opening reaction of one of the two phthalimide units of the HL1 ligand, affording carbinolamide and amide functionalities within one ligand set. The developed methodology characterizes an ample substrate scope. The selective amidation reactions of the carbonyl groups have been realized for a series of analogous ligands HL2-HL7. Density functional theory calculations were employed to disclose the mechanisms for the formation of 1-7, and the details for the selective ring-opening reactions of the phthalimide unit were uncovered.

Facile access to 1,3-diketones by gold(i)-catalyzed regioselective hydration of ynones.

A facile and efficient synthesis of 1,3-diketones was developed by the gold(i)-catalyzed regioselective hydration of ynones at room temperature. This methodology employed 2.5 mol% of PPh3AuCl and 3 mol% of AgOTf as a simple catalytic system without any special phosphine ligand and was compatible with a wide range of substrates, giving rise to 1,3-diaryl, 1-alkyl-3-aryl-, and 1,3-dialkyl-1,3-diketones in up to quantitative yields in open flask reactions. This methodology could be readily scaled up to gram-scales.

Direct C-S bond formation via C-O bond activation of phenols in a crossover Pd/Cu dual-metal catalysis system.

A dual-metal catalysis system including a newly prepared nanoparticle [SiO2@organic-linker(OL)@Pd(II)] and CuI was introduced with ultra-high catalytic activity (high turnover number (TON), up to 19 000) to a one-pot and odorless synthesis of unsymmetrical aryl sulfides by crossover C-S bond formation. The reaction proceeds via C-O bond activation of phenols and direct C-S bond formation in the presence of S8 as an oddorless sulfur source and aryl boronic acids under mild conditions (room temperature). The catalyst could be recycled up to five times without an obvious change in its activity.

Heteroatom-Doped Porous Carbon Materials with Unprecedented High Volumetric Capacitive Performance.

The design of carbon-based materials with a high mass density and large porosity has always been a challenging goal, since they fulfill the demands of next-generation supercapacitors and other electrochemical devices. We report a new class of high-density heteroatom-doped porous carbon that can be used as an aqueous-based supercapacitor material. The material was synthesized by an in situ dehalogenation reaction between a halogenated conjugated diene and nitrogen-containing nucleophiles. Under the given conditions, pyridinium salts can only continue to perform the dehalogenation if there is residue water remaining from the starting materials. The obtained carbon materials are highly doped by various heteroatoms, leading to high densities, abundant multimodal pores, and an excellent volumetric capacitive performance. Porous carbon tri-doped with nitrogen, phosphorous, and oxygen exhibits a high packing density (2.13 g cm-3 ) and an exceptional volumetric energy density (36.8 Wh L-1 ) in alkaline electrolytes, making it competitive to even some Ni-MH cells.

Porous Gold Nanoshells on Functional NH2 -MOFs: Facile Synthesis and Designable Platforms for Cancer Multiple Therapy.

AuroShell nanoparticles (sealed gold nanoshell on silica) are the only inorganic materials that are approved for clinical trial for photothermal ablation of solid tumors. Based on that, porous gold nanoshell structures are thus critical for cancer multiple theranostics in the future owing to their inherent cargo-loading ability. Nevertheless, adjusting the diverse experimental parameters of the reported procedures to obtain porous gold nanoshell structures is challenging. Herein, a series of amino-functionalized porous metal-organic frameworks (NH2 -MOFs) nanoparticles are uncovered as superior templates for porous gold nanoshell deposition (NH2 -MOFs@Aushell ) by means of a more facile and general one-step method, which combines the enriched functionalities of NH2 -MOFs with those of porous gold nanoshells. Moreover, in order to illustrate the promising applications of this method in biomedicine, platinum nanozymes-encapsulated NH2 -MOFs are further designed with porous gold nanoshell coating and photosensitizer chlorin e6 (Ce6)-loaded nanoparticles with continuous O2 -evolving ability (Pt@UiO-66-NH2 @Aushell -Ce6). The combination of photodynamic and photothermal therapy is then carried out both in vitro and in vivo, achieving excellent synergistic therapeutic outcomes. Therefore, this work not only presents a facile strategy to fabricate functionalized porous gold nanoshell structures, but also illustrates an excellent synergistic tumor therapy strategy.

A Flexible Caterpillar-Like Gold Nanoparticle Assemblies with Ultrasmall Nanogaps for Enhanced Dual-Modal Imaging and Photothermal Therapy.

Gold nanoparticle (AuNP) assemblies (GNAs) have attracted attention since enhanced coupling plasmonic resonance (CPR) emerged in the nanogap between coupling AuNPs. For one dimensional GNAs (1D-GNAs), most CPR from the nanogaps could be easily activated by electromagnetic waves and generate drastically enhanced CPR because the nanogaps between coupling AuNPs are linearly distributed in the 1D-GNAs. The reported studies focus on the synthesis of 1D-GNAs and fundamental exploration of CPR. There are still problems which impede further applications in nanomedicine, such as big size (>500 nm), poor water solubility, and/or poor stability. In this study, a kind of 1D flexible caterpillar-like GNAs (CL-GNAs) with ultrasmall nanogaps, good water solubility, and good stability is developed. The CL-GNAs have a flexible structure that can randomly move to change their morphology, which is rarely reported. Numerous ultrasmall nanogaps (<1 nm) are linearly distributed along the structure of CL-GNAs and generate enhanced CPR. The toxicity assessments in vitro and vivo respectively demonstrate that CL-GNAs have a low cytotoxicity and good biocompatibility. The CL-GNAs can be used as an efficient photothermal agent for photothermal therapy, a probe for Raman imaging and photothermal imaging.

Consecutive Lossen rearrangement/transamidation reaction of hydroxamic acids under catalyst- and additive-free conditions.

The Lossen rearrangement is a classic process for transforming activated hydroxamic acids into isocyanate under basic or thermal conditions. In the current report we disclosed a consecutive Lossen rearrangement/transamidation reaction in which unactivated hydroxamic acids were converted into N-substituted formamides in a one-pot manner under catalyst- and additive-free conditions. One feature of this novel transformation is that the formamide plays triple roles in the reaction by acting as a readily available solvent, a promoter for additive-free Lossen rearrangement, and a source of the formyl group in the final products. Acyl groups other than formyl could also be introduced into the product when changing the solvent to other low molecular weight aliphatic amide derivatives. The solvent-promoted Lossen rearrangement was better understood by DFT calculations, and the intermediacy of isocyanate and amine was supported well by experiments, in which the desired products were obtained in excellent yields under similar conditions. Not only monosubstituted formamides were synthesized from hydroxamic acids, but also N,N-disubstituted formamides were obtained when secondary amines were used as precursors.

Cyclization of Ynamide-Tethered 1,3,8-Triynes.

A facile thermal cyclization of ynamide-tethered 1,3,8-triynes to form a 3,5,6,7-tetrahydro-1H-pyrano[3,4-c]pyridine skeleton is described. Although the mechanism of this unusual reaction has yet to be defined, the formation of either a strained keteniminium or a biradical intermediate followed by a 1,5-hydride or -hydrogen shift is tentatively proposed as the key elementary steps in the reaction sequence. Appropriate electronic activation at the carbon center donating a hydride or hydrogen is crucial for successful cyclization.

Transfer Hydro-dehalogenation of Organic Halides Catalyzed by Ruthenium(II) Complex.

A simple and efficient Ru(II)-catalyzed transfer hydro-dehalogenation of organic halides using 2-propanol solvent as the hydride source was reported. This methodology is applicable for hydro-dehalogenation of a variety of aromatic halides and α-haloesters and amides without additional ligand, and quantitative yields were achieved in many cases. The potential synthetic application of this method was demonstrated by efficient gram-scale transformation with catalyst loading as low as 0.5 mol %.

Computational Revisit to the ß-Carbon Elimination Step in Rh(III)-Catalyzed C-H Activation/Cycloaddition Reactions of N-Phenoxyacetamide and Cyclopropenes.

This computational study uncovered the origin of the contradicting results in two recent DFT studies of the Rh(III)-catalyzed C-H activation/cycloaddition reactions between N-phenoxyacetamide and cyclopropenes. It was found that the ß-carbon elimination of the tricyclic intermediate occurs very faciely via a conformer in which the opening of the three-membered ring is trans to the Cp* ligand so that the steric repulsion between the two moieties is avoided. Thus, the conclusions of our previous study were reconfirmed.