Construction of C-P Bonds from Free Cyclobutanone Oximes and Chlorophosphines via Radical-Radical Coupling.

Herein, we report a catalyst-free reaction of cyclobutanone oximes with chlorophosphines (R2PCl), which forms a fragile C═N-O-PR2 species that undergoes N-O homolysis, fragmentation, and radical-radical coupling, leading to the formation of cyano-containing phosphine oxides in good yields. The reaction features an in situ activation of cyclobutanone oximes for radical generation, in which R2PCl plays a dual role as both an activator and a reactant.

Nitroalkanes as thioacyl equivalents to access thioamides and thiopeptides.

Thioamides are an important, but a largely underexplored class of amide bioisostere in peptides. Replacement of oxoamide units with thioamides in peptide therapeutics is a valuable tactic to improve biological activity and resistance to enzymatic hydrolysis. This tactic, however, has been hampered by insufficient methods to introduce thioamide bonds into peptide or protein backbones in a site-specific and stereo-retentive fashion. In this work, we developed an efficient and mild thioacylation method to react nitroalkanes with amines directly in the presence of elemental sulfur and sodium sulfide to form a diverse range of thioamides in high yields. Notably, this convenient method can be employed for the controlled thioamide coupling of multifunctionalized peptides without epimerization of stereocenters, including the late stage thioacylation of advanced compounds of biological and medicinal interest. Experimental interrogation of postulated mechanisms currently supports the intermediacy of thioacyl species.

Phosphine-Catalyzed [3+2] Annulation of Hepta-2,3,5-trienedioates with Alkenes for the Construction of Exocyclic Olefinic Cyclopentenes.

Hepta-2,3,5-trienedioates 1 have been employed as substrates to explore Lewis base-catalyzed annulation reactions. This leads to the discovery of a phosphine-catalyzed [3+2] annulation of 1 with electron-deficient alkenes for the construction of exocyclic olefinic cyclopentenes in good yields and moderate E:Z ratios under mild conditions. The annulation is believed to proceed in a tandem [3+2] cyclization and double bond migration in which the ε-ester is crucial to both processes. This reaction also showcases a substrate-controlled divergent reactivity compared to that of a previous report.

Improved simultaneous nitrification-denitrification in fixed-bed baffled bioreactors treating mariculture wastewater: Performance and microbial community behaviors.

As mariculture develops, wastewater treatment becomes crucial. In this study, fixed-bed baffled reactors (FBRs) packed with carbon fiber (CFBR) or polyurethane (PFBR) as biofilm carriers were used for mariculture wastewater treatment. Under salinity shocks between 0.10 and 30.00 g/L, the reactors showed efficient and stable nitrogen removal capacities, and the maximum NH4+-N removal rates were 107.31 and 105.42 mg/(L·d) for CFBR and PFBR, respectively, with an initial NH4+-N concentration of 120.00 mg/L. Further, in the independent aerobic chambers of the FBRs for nitrogen removal, taxa enrichment varied depending on the biofilm carrier, and the assembly process was more deterministic in CFBR than in PFBR. Two distinct clusters representing the spatial distribution of the adhering and deposited sludge in CFBR and the front and rear compartments in PFBR were noted. Furthermore, microbial interactions were more numerous and stable in CFBR. These findings improve the application prospects of FBRs in mariculture wastewater treatment.

Phosphine-Catalyzed Stereoselective Ring-Opening Addition of Cyclopropenones with Nucleophiles.

A phosphine-catalyzed ring-opening addition reaction of cyclopropenones with a variety of nucleophiles (NuH), including oxygen-, nitrogen-, sulfur-, and carbon-based ones, has been investigated, which produces potentially useful α,ß-unsaturated carbonyl derivatives in high yields (up to 99%), high regioselectivity, and exclusive E-selectivity. The reaction proceeds in high efficiency under very mild conditions using only 1 mol % PPh3 as the catalyst at room temperature. The method is also amenable for the synthesis of deuterated alkenes when deuterated nucleophiles (NuD) are employed. The mechanism is investigated by experiments and DFT calculations, which suggests an α-ketenyl phosphorus ylide as a key intermediate in the catalytic cycle that captures the nucleophiles in a stereoselective manner.

Synthesis of Phosphinic Amides from Chlorophosphines and Hydroxyl Amines via P(III) to P(V) Rearrangement.

Phosphoranyl radicals are essential mediators to bring about new radicals but often produce a stoichiometric amount of phosphine oxide/sulfide waste. Herein, we devised a phosphorus-containing species as a radical precursor, but without the generation of phosphorus waste. Accordingly, a catalyst-free synthesis of phosphinic amides from hydroxyl amines and chlorophosphines via P(III) to P(V) rearrangement is described. Mechanistically, it may involve the initial formation of a R2N-O-PR2 species that undergoes homolysis of N-O bonds and subsequent radical recombination.

A Robust Switchable Oil-In-Water Emulsion Stabilized by Electrostatic Repulsions between Surfactant and Similarly Charged Carbon Dots.

How to control the stability of oil-in-water (O/W) emulsions is one of the main topics for scientists working in colloidal systems. Recently, carbon dots (CDs) have received great interest as smart materials because of their excellent physicochemical properties and versatile applications. Herein, for the first time, advanced and switchable O/W emulsions are presented that are stabilized by the synergistic effect of cationic surfactant cetyltrimethylammonium bromide CTAB (emulsifier) and similarly charged CDs (stabilizer). In the formulated emulsion, the cationic surfactant molecules are adsorbed at the oil and water interface to decrease the interfacial tension and enrich the drops with a positive charge to ensure intensive electrostatic repulsions among them. On the contrary, cationic CDs are distributed in the water phase among the droplets to reduce the water secretion and prevent flocculation and droplet coalescence. The stabilizing effect is found to be universal for emulsions of a range of oil phases. Furthermore, the formulated emulsion is found to be switchable between "stable" and "unstable" modes by adding an equivalent of anionic surfactant sodium dodecyl benzene sulphonate (SDBS). The stabilized and switchable O/W emulsions are believed to have wide practical applications in water purification, pharmaceuticals, protein recognition, as well as catalysis.

Phosphine-catalyzed activation of cyclopropenones: a versatile C3 synthon for (3+2) annulations with unsaturated electrophiles.

We herein report a phosphine-catalyzed (3 + 2) annulation of cyclopropenones with a wide variety of electrophilic π systems, including aldehydes, ketoesters, imines, isocyanates, and carbodiimides, offering products of butenolides, butyrolactams, maleimides, and iminomaleimides, respectively, in high yields with broad substrate scope. An α-ketenyl phosphorous ylide is validated as the key intermediate, which undergoes preferential catalytic cyclization with aldehydes rather than stoichiometric Wittig olefinations. This phosphine-catalyzed activation of cyclopropenones thus supplies a versatile C3 synthon for formal cycloadditon reactions.

Self-assembled core-shell clusters in deep eutectic solvents based on tetra-n-alkylammonium cations for high dissolution of strongly hydrogen-bonded small molecules.

Strongly hydrogen-bonded compounds such as 1,3,5-triamino-2,4,6­trinitrobenzene (TATB, an important insensitive high explosive) have excellent stability, but poor solubilities to limit their recrystallization, purification and recycling. In this study, core-shell clusters based on symmetrical tetra-n-alkylammonium [TTA]+ are designed to provide an inner cavity to incorporate TATB, and thus the clusters can separate TATB from original hydrogen-bonded networks to increase largely the solubility. Based on this design, deep eutectic solvents (DESs) based on [TTA]+ cations are first developed to yield self-assembled core-shell clusters for solubilizing TATB. Ninety-nine DESs based on [TTA]+ were prepared by combining with halide ions and hydrogen bond donors, and TATB's solubility increases with the formation of core-shell clusters. Tetrabutyl ammonium ([TBA]+ )-based DES (CS-1) displays excellent dissolution toward TATB. Room-temperature solubility of TATB in CS-1 with 32.88 mg/mL is about 10 times higher than recently reported ionic liquids and approximately 470 times higher than DMSO. Compared to traditional solvents, CS-1 shows economical and high dissolution ability toward TATB. The dissolution mechanism is demonstrated by experimental characterizations and theoretical calculations. After forming Zundel-type complexes between TATB and F-, the complexes as the core are surrounded by [TBA]+ as the shell to yield core-shell clusters through self-assembly of electrostatic interaction.

Spatially-directed magnetic molecularly imprinted polymers with good anti-interference for simultaneous enrichment and detection of dual disease-related bio-indicators.

As the changes of biomarkers directly reflect the occurrence of degenerative diseases, accurate detection of biomarkers is of great significance for disease diagnosis and control. However, single index detection has high uncertainties to accurately reflect the pathological characteristics because of the complexity of the human internal environment and the extremely trace concentration of indicators. To this end, a method for simultaneous detection of dual-biomarkers based on anti-interference magnetic molecularly imprinted polymers (D-mag-MIPs) is thereby proposed, and successfully applied in human urine analysis for the detection of Parkinson's disease bio-indicators 4-dihydroxyphenylacetic acid (DOPAC) and dopamine (DA). In this work, carboxyl functionalized ferric oxide served as a magnetic core, laying a solid foundation for batch detection. Hyperbranched polyethylenimine, whose abundant amino groups can provide multiple interaction forces to templates with high affinity, is employed as a functional monomer. Relative to single-template MIPs, D-mag-MIPs achieve the detection of dual bio-indicators in a one-time test, reducing the false positive result probability and enhancing the detection accuracy. The proposed methodology has been evaluated to exhibit good anti-interference, satisfactory precision, low detection limits, wide linear ranges and fast batch detection for DA and DOPAC. This work thus offers an alternative and efficient pathway for convenient batch detection of dual bio-indicators from biofluids at once.

DABCO-Catalyzed [4 + 2] Annulation of 5-Methylenehex-2-ynedioates with Electron-Deficient Alkenes.

Herein, we describe a DABCO-catalyzed [4 + 2] annulation between 5-methylenehex-2-ynedioates and electron-deficient olefins to afford functionalized cyclohexadienes in good yields under mild conditions. The use of ß- and ε-carbons of the substrates for C-C bond formation is distinct from previous reports showing a substrate-controlled divergent reactivity. The annulation is believed to proceed in domino cyclization initiated by a cross Rauhut-Currier reaction.

Ru(II)-Catalyzed Difunctional Pyridyloxy-Directed Regio- and Stereospecific Addition of Carboxylic Acids to Internal Alkynes.

A highly efficient Ru(II)-catalyzed regio- and stereospecific hydro-oxycarbonylation of unsymmetrical internal alkynes bearing a difunctional 2-pyridyloxy directing group with carboxylic acids has been developed, which provides allylic (Z)-enol esters in good to excellent yields with a broad substrate scope under mild conditions. The difunctional directing group can be diversely derivatized, particularly undergoing allylic substitution with various nucleophiles to afford ß-functionalized (Z)-enol esters without directing groups.

Rapid Construction of Hexacyclic Indolines via the Ru(II)-Catalyzed C-H Activation Initiated Cascade Cyclization of Phenidones with Enynones.

A highly efficient cascade cyclization of phenidones and enynones has been developed via a Ru(II)-catalyzed C-H activation initiated indole formation/Diels-Alder reaction/iminium ion cyclization sequence, which afforded hexacyclic indolines as single diastereomer in good to excellent yields with a broad substrate scope under mild conditions. The reaction features the simultaneous generation of five new chemical bonds and four new rings in one pot, providing a rapid and concise approach toward polycyclic indoline alkaloids and their analogues.

Phosphine-Catalyzed Internal Redox [4 + 2] Annulation between 1,4-Enynoates and Electron-Deficient Alkenes.

Herein we describe a phosphine-catalyzed internal redox [4 + 2] annulation of 1,4-enynoates with electron-deficient alkenes, in which the γ- and φ-C(sp3)-H of the enynoates are formally oxidized for the annulation while the alkynyl moiety is converted to an alkene. The reaction offers an efficient synthesis of highly functionalized cyclohexenes in moderate to good yields with exclusive regioselectivity and high diastereoselectivity under mild conditions.

Synthesis of Indole-Fused Oxepines via C-H Activation Initiated Diastereoselective [5 + 2] Annulation of Indoles with 1,6-Enynes.

A rhodium-catalyzed diastereoselective formal [5 + 2] annulation of indoles with cyclohexadienone-containing 1,6-enynes has been established via indole 2,3-difunctionalization. The reaction, probably proceeding through tandem indole C2-H alkenylation and intramolecular Friedel-Crafts alkylation relay, provides rapid construction of indole-fused oxepines in good to excellent yields with a broad substrate scope. This method also features concomitant construction of cis-hydrobenzo[b] oxepine scaffolds, a core unit found in numerous natural products of important biological activities.

Phosphine-Catalyzed Cross-Coupling of Benzyl Halides and Fumarates.

A phosphine-catalyzed olefinic cross-coupling between benzyl halides and fumarates is described, which affords trisubstituted alkenes in good yields and excellent E-selectivity under metal-free conditions. Mechanistic studies suggest a catalytic cycle involving phosphorus ylide formation, Michael addition, water-assisted hydrogen transfer, and phosphine elimination.

Catalyst-Free [3 + 3] Annulation/Oxidation of Cyclic Amidines with Activated Olefins: When the Substrate Olefin Is Also an Oxidant.

Herein we describe a catalyst-free regioselective [3 + 3] annulation/oxidation reaction of cyclic amidines such as DBU (1,8-diazabicyclo(5.4.0)undec-7-ene) and DBN (1,5-diazabicyclo(4.3.0)non-5-ene) with activated olefins, i.e., 2-arylidenemalononitriles and 2-cyano-3-aryl acrylates, to afford tricyclic 2-pyridones and pyridin-2(1H)-imines, respectively. The mechanism has been proposed based on DFT calculations. In the reaction, the cyclic amidines serve as C,N-bisnucleophiles for the cyclization, while the olefins play a dual role by acting as both reactants and oxidants.

Synthesis of Cyclopentadienes for Cyclopentadienyl Ligands via Cp*RhIII-Catalyzed Formal sp3 C-H Activation/Spiroannulations.

An efficient Cp*RhIII-catalyzed formal C(sp3)-H activation/spiroannulation of alkylidene Meldrum's acids with alkynes has been developed using catalytical Cu(OAc)2 and air as the oxidant. This reaction demonstrates a new and straightforward approach to spirocyclopentadienes with Meldrum's acid moieties in good to excellent yields under mild reaction conditions with a broad substrate scope. Notably, this protocol provides a novel and straightforward approach to cyclopentadienes with various substitution patterns and the corresponding cyclopentadienyl-type ligands from simple substrates.

Multicomponent benzannulation of allylic P-ylides with isocyanates or aldehydes for construction of anilines and biaryls.

The reactivity of allylic phosphorus ylides generated in situ from alkoxycarbonylmethylenephosphoranes and propiolates is investigated toward isocyanates and aromatic aldehydes, which leads to one-pot multicomponent benzannulations for efficient synthesis of polysubstituted anilines and biaryls, respectively. The mechanism may involve a tandem [2+2] cycloaddition/fragmentation/Wittig/cyclization/elimination/aromatization sequence.

A three-component reaction of phosphorus ylides with isocyanates: facile synthesis of 2-amino-3-carboxylate-4-quinolones.

A three-component reaction between one molecule of phosphorus ylides (P-ylides) and two molecules of isocyanates for the rapid assembly of 2-amino-3-carboxylate-4-quinolones is described. The mechanism may involve the addition of a P-ylide to an isocyanate followed by 1,3-H shift to form a carbamoyl stabilized P-ylide. The intermediate then reacts with another aryl isocyanate via Wittig/ketenimine-ketene rearrangement/6π-electrocyclization/1,3-H shift to finally afford the 4-quinolones.