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A novel approach for the synthesis of 1,1,4,5-tetrasubstituted phthalans is developed via a tandem palladium-catalyzed Sonogashira coupling/propargyl-allenyl isomerization/pentadehydro-Diels-Alder cyclization/regioselective nucleophilic addition sequence. The reaction shows good functional tolerance and provides a wide variety of substituted phthalans in moderate to high yields from haloarenes, triynes, and protic nucleophiles, such as amines and alcohols, under very mild conditions.

The value of functional pyrrolidines in the fields of biology, pharmacology, catalysis, and natural product synthesis stimulates an intensive interest in developing new synthetic methods for this class of compounds, and direct functionalization of the simple pyrrolidine represents an attractive and effective approach. Herein, a metal-free protocol for direct N-arylation and α-functionalization of pyrrolidine via redox-neutral three-component reactions is reported, in which p-quinol ethers or p-quinone monoacetals serve as the arylation components and the formal oxidants for α-functionalization of pyrrolidine.

The tandem decarboxylative condensation-dimerization reaction of l-proline with 2,5-cyclohexadienones including p-quinone monoacetals, p-quinol ethers, and p-quinols is reported to provide a concise and rapid synthesis of octahydro-dipyrroloquinoline compounds. The reaction features the use of cost-effective and readily available starting materials, high efficiency, metal-free and green reaction conditions. The reaction is applied to the synthesis of incargranine B aglycone. The discovery of this reaction may suggest a biosynthetic pathway from 2,5-cyclohexadienones and proline for natural ingredients containing pyrroloquinoline moieties.

The one-pot three-component reaction of p-quinone monoacetals (or p-quinol ethers), L-proline and naphthols is developed for the synthesis of N-aryl-2-arylpyrrolidines under mild conditions with high chemo- and regioselectivity. The reaction may involve multiple processes including condensation, decarboxylation and demethoxylation for the the generation of N-arylated 3,4-dihydro-2H-pyrrolium followed by controllable capture by naphthols. In the absence of a naphthol, p-quinone monoacetal coupled with L-proline to form a complex dipyrroloquinoline product.

The three-component reactions of α-amino acids, p-quinone monoacetals (or p-quinol ethers), and diarylphosphine oxides have been developed for the synthesis of 3-(diarylphosphinyl) anilides and N-aryl-2-diarylphosphinylpyrrolidines. The transformations may involve the in situ generation of conjugated azomethine ylides or 2-azaallyl anion species from the reaction of α-amino acids and p-quinone monoacetals, which are further trapped by diarylphosphine oxides.

Pyridotriazoles are utilized as robust building blocks to access α-secondary and α-tertiary pyridines via the development of a simple yet practically useful metal-free denitrogenative C-C cross-coupling with boronic acids. The reaction shows a high level of functional tolerance, broad substrate scope, and facile scalability. The synthetic potential of the method is demonstrated by the strurctural modification of a bioactive molecule and concise synthesis of pheniramine analogs.

The zinc triflate-catalyzed highly regioselective C-P cross coupling reaction of p-quinol ethers with secondary phosphine oxides is reported. The reaction provides a facile alternative method for the synthesis of 2-phosphinylphenols in good to high yields. Mechanistically, zinc triflate may serve as an oxophilic σ-Lewis acid to activate the C-O bond in p-quinol ether first. Then the regioselective attack of the phosphorus nucleophile at the α-carbon position takes place to form the C-P bond and give the product. In addition, α-alkynyl substituted p-quinol ethers also react with secondary phosphine oxides in the same reaction mode to give 6-alkynyl 2-phosphinylphenols in the presence of the zinc catalyst.

A Cu(MeCN)4BF4-catalyzed dehydrative reaction of 1-(2-hydroxyphenyl)propargyl alcohols with diarylphosphine oxides has been developed to provide an efficient synthesis of phosphorylated benzofurans in good to high yields. In the presence of a catalytic amount of an organic base, a variety of H-phosphonates and H-phosphinates can also be employed as good substrates to produce the corresponding products in moderate yields. The reaction has significant economical and ecological advantages since the formation of a new Csp3−P bond and the benzofuran framwork could both be achieved using an inexpensive copper catalyst with water produced as the sole byproduct. The synthetic transformations of the product have also been demonstrated.

A highly selective Ph3P-mediated C(α)–P coupling reaction of quinone monoacetals with secondary phosphine oxides is developed to provide an effective method for the synthesis of a wide array of ortho-phosphinylphenols in good to excellent yields. This protocol can be adopted for scale-up synthesis directly from cheap and abundant phenols, and the products can be easily obtained in high yields by simple filtration without the use of organic extraction or chromatography.

The cadmium(II) chloride-catalyzed dehydrative C−P cross-coupling reaction of propargyl alcohols with diarylphosphine oxides is reported. Several propargyl alcohols including those bearing the sterically demanding tert-butyl group at the triple bond terminus can be used as good substrates in the reaction to produce the corresponding allenylphosphine oxides in good to high yields in acetonitrile at 100 °C. The reaction can also be easily scaled up to a gram-scale synthesis. A mechanism study indicates that the reaction may proceed through a process of propargylic substitution to generate phosphonite intermediates followed by [2,3] sigmatropic rearrangement to produce the allenyl products, rather than through a common allenylative substitution resulting from P-nucleophilicity.

The highly regioselective nucleophilic ring opening of propargyl epoxides by P(O)H compounds based on a Ag catalyst is reported. A variety of P(O)H compounds including H-phosphonates, H-phosphinates and diarylphosphine oxides can be used to produce 4-phosphoryl 2,3-allenols under mild conditions. The stereoselective synthesis of 1-phosphoryl 1,3-butadienes from 4-phosphoryl 2,3-allenols and organoboronic acids via a Pd-catalyzed coupling reaction is also described.

2,4,5-Trifluorobromobenzene is a valuable synthetic intermediate with important applications in pharmaceutical industry. We report a continuous microflow process for the synthesis of 2,4,5-trifluorobromobenzene via Gattermann reaction in this paper. The microflow system is easily assembled by a simple T-micromixer, microchannel reactors and several pumps. The use of this system facilitated the diazotization reaction of 2,4,5-trifluoroaniline with HBr and NaNO 2 to produce the thermally unstable 2,4,5-trifluorophenyl diazonium salts in seconds, which then react with HBr at the catalysis of copper powder to obtain 2,4,5-trifluorobromobenzene. The aqueous HBr containing copper powder was added and stirred for 30 min at 70 °C in the stirred vessel. And then, the CuBr in situ was given and performed a quench-type reaction as catalyst. The influence of the reaction parameters on the diazotization reaction steps was examined and discussed in microreactors. The microflow system had the capacity to promote efficient mass- and heat-transfer and shorten the reaction time. On this basis, the kilogram-scale production of 2,4,5-trifluorobromobenzene was realized in a self-made scale-up microreactor by numbering-up of micromixers and microchannels.

The nucleophilic ring opening reaction of propargyl epoxides by amines based on a silver catalyst is presented. The reaction takes place under mild conditions and features a high regioselectivity to provide an effective method for the synthesis of 2-amino homopropargyl alcohols in moderate to high yields.

2,4,5-Trifluorobromobenzene is a valuable intermediate with important application in the synthesis of biologically active peptides and fluorescent reagents. A continuous-flow system has been successfully developed for the synthesis of 2,4,5-trifluorobromobenzene in a microreactor using FeBr3 as a catalyst, which is steadily generated in situ from the reaction of Br2 and Fe. The procedure is efficient and easy-to-handle, and 2,4,5-trifluorobromobenzene can be obtained within minutes in high yields.

A novel Cu-catalysed substitution reaction of propargyl acetates with P(O)H compounds is developed to afford allenylphosphoryl compounds via C-P bond coupling in high yields under mild conditions. A plausible mechanism involving the nucleophilic interception of the Cu-allenylidene intermediates is proposed.

A novel CuI-catalyzed cross-coupling of propargyl epoxides with P(O)H compounds is disclosed. The reaction proceeded efficiently under mild conditions to give 4-phosphoryl 2,3-allenols in good to high yields with excellent selectivity. The utility of the products was demonstrated and a plausible mechanism was also proposed.

Fluoride plays an important role in our daily life as it associates with a variety of biological and pathological processes. Hence, an analytic method that can detect fluoride ions under physiological conditions with high sensitivity and specificity, and fast response, is needed. Herein, we introduced a dioxetane-based chemiluminescent probe, CL-F, specifically designed for the detection of fluoride ions in physiological environment. The probe CL-F emitted strong green chemiluminescent light within 1 min when incubating with fluoride ions specifically. The linear range for sensing fluoride ions and limit of detection were determined to be 0–30 μM and 0.91 μM, respectively. The probe CL-F was then successfully applied in quantifying fluoride ions in toothpaste and in vivo imaging in living mice, demonstrating CL-F as a promising tool for sensing fluoride ion in vitro and in vivo.

A less expensive and more environmentally friendly Zn(OTf)2-catalyzed dehydrative coupling reaction of propargyl alcohols with diarylphosphine oxides is reported. The reaction takes place under mild and solvent free conditions, and features a high regioselectivity to provide an effective method for the synthesis of some diarylphosphinyl allenes in moderate to high yields.

A cationic gold(I)-catalyzed decarboxylative etherification of propargyl carbonates to selectively produce propargyl ethers is reported. In the reaction the gold(I) catalyst shows a distinct σ-Lewis acidity rather than the commonly observed π-Lewis acidity, and thus catalyzes the decarboxylation of a variety of propargyl carbonates to give the corresponding propargyl ethers with high selectivity. This reaction represents a rare example of the tunable reactivity of cationic gold(I) complexes between σ-Lewis acidity and π-Lewis acidity.

2,4,5-Trifluorobenzoic acid is a valuable synthetic intermediate with important application in pharmaceutical industry and material science. In this paper, we report a facile continuous microflow process for the synthesis of 2,4,5-trifluorobenzoic acid via the generation of an unstable aryl-Grignard reagent followed by its reaction with gaseous CO2. The microflow system is easily assembled by a simple T-micromixer, a commercial available falling film microreactor, tube microreactor and several pumps. The use of a composed T-micromixer and tube microreactor facilitates the Grignard exchange reaction of 2,4,5-trifluorobromobenzene with ethylmagnesium bromide producing 2,4,5-trifluorophenylmagnesium bromide almost in quantitative yield, and the use of the falling film microreactor enables a highly efficient gas–liquid reaction of the resultant Grignard reagent with CO2 under an atmosphere pressure, which ultimately gave the product 2,4,5-trifluorobenzoic acid in high yield with high purity after a simple and extractive workup. The influence of reaction parameters on the two steps in microreactors was discussed.

A novel Pd-catalyzed tandem reaction involving hydroalkynylation, isomerization, Diels–Alder cycloaddition and aromatization reaction to produce phthalan derivatives in moderate yields is reported. The reaction is atom economical and occurs in a highly ordered fashion. The reaction mechanism is discussed.

The amino-modified mesoporous material SBA-15 (NH2-SBA-15) was prepared via co-condensation of tetraethylorthosilicate with 3-aminopropyltriethoxysilane in the presence of an amphiphilic triblock copolymer as a pore-directing agent under acidic conditions. The SBA-15-supported Cu Schiff-base complex (Cu-SBA-15) was then synthesized by condensation of salicylaldehyde with NH2-SBA-15, followed by the addition of a solution of Cu(NO3)2. The supported complex was systematically characterized by elemental analysis, inductive coupled high frequency plasma atomic emission spectrometry, powder X-ray diffraction, Fourier transform infrared spectroscopy, ultraviolet-visible spectroscopy, field scanning electron microscopy, transmission electron microscopy, N2 absorption-desorption, and thermo gravimetric analysis, and was used as the catalyst for the selective oxidation of styrene to benzaldehyde. The influence of the reaction parameters was assessed. The maximum conversion of styrene was 84.4% and the selectivity for benzaldehyde was 83.9%, when the reaction was conducted with a 2:1 molar ratio of H2O2:styrene in the presence of 3.8 wt% catalyst at 100 °C for 8 h. The TOF was 261.1 h−1, and the catalyst could be used three times without significant loss of activity. The uniformly sized pore channels, high specific surface area, and well-distributed active centers of the catalyst may contribute to the high activity.

Present work demonstrated the facile preparation of silica microspheres with various structures (solid, hollow, hollow with a hole and filbert-like solid). These were prepared by first forming monodisperse silica sol droplets in a simple microfluidic device, followed by extracting the solvent from the droplets in an extractant or at the interface between the extractant and liquid paraffin at different conditions. The effect of different extractants and extracting temperature was investigated. The products were characterized by optical microscope and scanning electron microscope. Extraction in fatty acid methyl ester (FAME) at room temperature led to formation of solid silica microspheres, while extraction at the interface between FAME and liquid paraffin at 60 °C resulted in formation of hollow silica microspheres. Use of mixture of castor oil (CO) and dimethyl carbonate (DMC) as extractant resulted in formation of hollow silica microspheres with a hole on the surface, whereas increase in the DMC content in extracting medium led to formation of filbert-like silica solid microspheres. Change in size of cavity and hole was studied by changing the extracting temperature. The formation process and mechanism of these silica microspheres are proposed based on the diffusion rate. The relationship between the size of the microspheres and the state of the droplet at the interface is correlated.

The reaction of P(O)-H compounds with p-quinones could proceed through either 1,4- or 1,6-addition pathways by employing different additives to selectively give the corresponding C- and O-phosphoryl hydroquinone derivatives in good yields. Oxidative double 1,4-addition of P(O)-H compounds to p-quinones was also achieved by tuning the solvent, affording a facile synthesis of bis-substituted hydroquinones with phosphorus functionality. Further studies on these reactions by using optically active H-phosphinates showed that all addition reactions took place stereospecifically with retention of configuration at the phosphorus center. The findings lead to the establishment of a divergent method for the synthesis of C- and O-phosphoryl hydroquinone derivatives from easily available P(O)-H compounds.

A facile, highly stereo- and regioselective hydrometalation of alkynes generating alkenylmetal complex is disclosed for the first time from a reaction of alkyne, carboxylic acid, and a zerovalent group 10 transition metal complex M(PEt(3))(4) (M = Ni, Pd, Pt). A mechanistic study showed that the hydrometalation does not proceed via the reaction of alkyne with a hydridometal generated by the protonation of a carboxylic acid with Pt(PEt(3))(4), but proceeds via a reaction of an alkyne coordinate metal complex with the acid. This finding clarifies the long proposed reaction mechanism that operates via the generation of an alkenylpalladium intermediate and subsequent transformation of this complex in a variety of reactions catalyzed by a combination of Brϕnsted acid and Pd(0) complex. This finding also leads to the disclosure of an unprecedented reduction of alkynes with formic acid that can selectively produce cis-, trans-alkenes and alkanes by slightly tuning the conditions.

In this paper, we report a novel sequential reaction sequence consisting of a series of processes including Sonogashira coupling, propargyl-allenyl isomerization, [3 + 2] cycloaddition, denitrogenation, and highly selective biradical coupling reaction, providing an efficient synthesis of fused polycyclic pyrrole derivatives. The reaction features one C-C bond and two C-N bonds formed to construct the pyrrole unit, together with two rings efficiently assembled in one stroke.

A stepwise process involving Sonogashira coupling, propargyl-allenyl isomerization and Schmittel cyclization has been realized, leading to an efficient synthesis of polycyclic fluorene derivatives from readily available starting materials. The reaction features the formation of three new carbon-carbon bonds to construct the benzene unit together with an efficient assembly of three or four rings in a single operative step.

A variety of dihydroisobenzofuran derivatives has been prepared in good yields via an interesting sequential reaction consisting of palladium-catalyzed coupling, propargyl-allenyl rearrangement, [4 + 2] cycloaddition and aromatization. A double-coupling, rearrangement, [4+2] cycloaddition and aromatization process is also described for the synthesis of more complex and diverse structures.

The nucleophilic addition of sodium azide to 1,2-allenyl esters can generate vinyl azides in excellent yields with excellent regio- and stereoselectivities. Moreover, pyrroles are synthesized using 1-allyllic 1,2-allenyl esters as substrates in t-BuOH at 65 degrees C. The sequential reaction for pyrroles is developed on the basis of a novel domino process involving nucleophilic addition, cycloaddition, denitrogenation, and aromatization.

In the catalyzed decarboxylative etherification of propargyl carbonates the gold(I) catalyst shows a distinct σ-acidity and propargyl ethers are furnished.

A novel Pd-catalyzed tandem reaction involving hydroalkynylation, isomerization, Diels–Alder cycloaddition and aromatization reaction to produce phthalan derivatives in moderate yields is reported. The reaction is atom economical and occurs in a highly ordered fashion. The reaction mechanism is discussed.

The new cascade reaction proceeds with high regio- and stereoselectivity, and tolerates a wide range of functionality and structural motifs.

An atom-economic tandem Pd(II)-catalyzed hydroalkynylation, alkyne-allene isomerization, and Diels–Alder cycloaddition is reported. The reaction employs readily available starting substrates, proceeds in a highly ordered fashion, features high regio- and stereoselectivity, and tolerates a wide range of functionality and structural motifs, thus offering an attractive strategy for producing new molecular complexity and diversity from easily available starting materials. A mechanistic study with density functional theoretical calculations was conducted to rationalize the observed stereoselectivity.