Palladium-Catalyzed Decarbonylative Michaelis-Arbuzov Reaction of Carboxylic Acids and Triaryl Phosphites.

A Pd-catalyzed decarbonylative Michaelis-Arbuzov reaction of carboxylic acids and triaryl phosphites for preparing aryl phosphonates under anhydride-free conditions has been reported. In this context, triaryl phosphites serve as both reagents for activating the carboxylic acids and substrates for the reaction. There have been no reports to date of efficient and direct methods for the in situ activation of carboxylic acids using triaryl phosphites. In comparison to known methods, this reaction avoids the use of organohalides and has an excellent functional group tolerance for the synthesis of various aryl phosphonates from triaryl phosphites and carboxylic acids. This reaction is scalable and applicable to the synthesis of aryl phosphonates featuring bioactive fragments.

Pd-Catalyzed Decarbonylative sp2 C-H Arylation: Construction of Five- and Six-Membered (Hetero)Cyclic Compounds.

The cyclic compounds have wide applications in the design and synthesis of drugs and materials; thus, their efficient construction attracts much attention from the synthetic community. In this letter, we report an efficient method for preparing cyclic compounds starting from the readily available carboxylic acids. This reaction takes place through intramolecular decarbonylative sp2 C-H arylation, enabling efficient synthesis of a wide range of five- and six-membered cyclic compounds. Both carbo- and heterocycles can be produced under the reaction conditions. Moreover, this reaction features a wide substrate scope with high functional group tolerance. The scale-up experiments also show its practicality in organic synthesis. Those experimental results indicate that this reaction would find wide applications in the synthetic community.

CuH-Catalyzed Reductive Coupling of Nitroarenes with Phosphine Oxides for the Direct Synthesis of Phosphamides.

A CuH-catalyzed reductive coupling of nitroarenes with phosphine oxides is developed, which produces a series of phosphamides in moderate to excellent yields with good functional group tolerance. Gram-scale synthesis and late-stage modification of nitro-aromatic functional molecule niclosamide are also successfully conducted. The mechanism study shows that the nitro group is transformed after being reduced to nitroso and a nucleophilic addition procedure is involved during the reaction.

Ligand-Free Iron-Catalyzed Construction of C-P Bonds via Phosphorylation of Alcohols: Synthesis of Phosphine Oxides and Phosphine Compounds.

An efficient method for the construction of C-P(V) and C-P(III) bonds via the iron-catalyzed phosphorylation of alcohols under ligand-free conditions is disclosed. This strategy represents a straightforward process to prepare a series of phosphine oxides and phosphine compounds in good to excellent yields from the readily available alcohols and P-H compounds. A plausible mechanism is also proposed. We anticipate that this mode of transforming simple alcohols would apply in chemical synthesis widely.

Palladium-Catalyzed Decarbonylative Annulation of 2-Arylbenzoic Acids with Internal Alkynes toward Phenanthrenes.

A palladium-catalyzed decarbonylative annulation of 2-arylbenzoic acids with internal alkynes via C(sp2)-H activation has been developed. A series of phenanthrenes were produced in moderate to good yield with good functional group tolerance. The mechanism study indicated that the C(sp2)-H activation should be the rate-determining step during the reaction.

Palladium-catalyzed and norbornene-mediated C-H amination and C-O alkenylation of aryl triflates.

The C-H amination and C-O alkenylation of aryl triflates was achieved through Pd/norbornene (NBE) cooperative catalysis. By this strategy, various ortho-alkenyl tertiary anilines including those bearing functional groups were produced in good to excellent yields. This reaction represents a new conversion model for phenoxides. It expands the scope of Catellani-type reactions and the application of phenoxides in organic synthesis.

A Novel Electrochemiluminescence Immunosensor Based on Resonance Energy Transfer between g-CN and NU-1000(Zr) for Ultrasensitive Detection of Ochratoxin A in Coffee.

In this study, an electrochemiluminescence (ECL) immunosensor based on nanobody heptamer and resonance energy transfer (RET) between g-C3N4 (g-CN) and NU-1000(Zr) was proposed for ultrasensitive ochratoxin A (OTA) detection. First, OTA heptamer fusion protein was prepared by fusing OTA-specific nanometric (Nb28) with a c-terminal fragment of C4 binding protein (C4bpα) (Nb28-C4bpα). Then, Nb28-C4bpα heptamer with the high affinity used as a molecular recognition probe, of which plenty of binding sites were provided for OTA-Apt-NU-1000(Zr) nanocomposites, thereby improving the immunosensors' sensitivity. In addition, the quantitative analysis of OTA can be achieved by using the signal quenching effect of NU-1000(Zr) on g-CN. As the concentration of OTA increases, the amount of OTA-Apt-NU-1000(Zr) fixed on the electrode surface decreases. RET between g-CN and NU-1000(Zr) is weakened leading to the increase of ECL signal. Thus, OTA content is indirectly proportional to ECL intensity. Based on the above principle, an ultra-sensitive and specific ECL immunosensor for OTA detection was constructed by using heptamer technology and RET between two nanomaterials, with a range from 0.1 pg/mL to 500 ng/mL, and the detection limit of only 33 fg/mL. The prepared ECL-RET immunosensor showed good performance and can be successfully used for the determination of OTA content in real coffee samples, suggesting that the nanobody polymerization strategy and the RET effect between NU-1000(Zr) and g-CN can provide an alternative for improving the sensitivity of important mycotoxin detection.

Palladium-Catalyzed Decarbonylative Cyanation of Carboxylic Acids with TMSCN.

The direct decarbonylative cyanation of benzoic acids with TMSCN was achieved through palladium catalysis. By this strategy, a wide range of nitriles including those with functional groups was synthesized in good to high yields. Moreover, this reaction applied to modifying bioactive molecules such as adapalene, probenecid, telmisartan, and 3-methylflavone-8-carboxylic acid. These results demonstrate that this new reaction has potential synthetic value in organic synthesis.

Nickel-Catalyzed Decarbonylative Thioetherification of Carboxylic Acids with Thiols.

A nickel-catalyzed decarbonylative thioetherification of carboxylic acids with thiols was developed. Under the reaction conditions, benzoic acids, cinnamic acids, and benzyl carboxylic acids coupled with various thiols including both aromatic and aliphatic ones produce the corresponding thioethers in up to 99% yields. Moreover, this reaction was applicable to the modification of bioactive molecules such as 3-methylflavone-8-carboxylic acid, probenecid, and flufenamic acid, and the synthesis of acaricide chlorbenside. These results well demonstrated the potential synthetic value of this new reaction in organic synthesis.

Base-promoted direct E-selective olefination of organoammonium salts with sulfones toward stilbenes and conjugated 1,3-dienes.

A base-promoted direct deaminative olefination of organoammonium salts was developed. Only mediated by KOtBu, a series of benzyl and cinnamyl ammonium salts reacted smoothly with sulfones, producing the valuable stilbenes and related 1,3-diene derivatives in good to high yields with good functional group tolerance and excellent E-selectivity. With this developed method, biologically active resveratrol and DMU-212 were also successfully prepared, which further demonstrates the practicality of this reaction.

Highly Chemoselective Transamidation of Unactivated Tertiary Amides by Electrophilic N-C(O) Activation by Amide-to-Acyl Iodide Re-routing.

The challenging transamidation of unactivated tertiary amides has been accomplished via cooperative acid/iodide catalysis. Most crucially, the method provides a novel manifold to re-route the reactivity of unactivated N,N-dialkyl amides through reactive acyl iodide intermediates, thus reverting the classical order of reactivity of carboxylic acid derivatives. This method provides a direct route to amide-to-amide bond interconversion with excellent chemoselectivity using equivalent amounts of amines. The combination of acid and iodide has been identified as the essential factor to activate the amide C-N bond through electrophilic catalytic activation, enabling the production of new desired transamidated products with wide substrate scope of both unactivated amides and amines, including late-stage functionalization of complex APIs (>80 examples). We anticipate that this powerful activation mode of unactivated amide bonds will find broad-ranging applications in chemical synthesis.

Gold nanoparticle-based colorimetric aptasensor for rapid detection of multiple mycotoxins in rice.

A novel, simple and rapid colorimetric aptasensor for multiple mycotoxins (ochratoxin A (OTA) and aflatoxin B1 (AFB1)) detection was developed using unmodified gold nanoparticles (AuNPs). In the work, the high affinities of OTA and AFB1 aptamers were employed as the recognition elements for the colorimetric determination of OTA and AFB1. In the absence of mycotoxins, the sulfhydryl-modified aptamers were directly adsorbed to the AuNP surface through Au-S bonds, further prohibiting the aggregation induced by a high concentration of salt, and the solutions remain red. In the presence of mycotoxins, the corresponding aptamer-target complexes were formed and the corresponding aptamers were detached from the surface of AuNPs, leading to the aggregation of AuNPs under the optimal salt solution and a color change. By spectroscopic quantitative analysis and visual analysis, the LODs of OTA and AFB1 were down to 0.005 ng mL-1 and 0.07 ng mL-1, respectively. Furthermore, the colorimetric aptasensor showed a high specificity in the presence of other interfering mycotoxins and metal ions. Finally, the developed aptasensor was applicable to detect OTA and AFB1 in rice samples with satisfactory performance. Our strategy has great potential for the rapid and sensitive detection of OTA and AFB1 for on-site analysis.

Electrochemiluminescence Immunosensor Based on Nanobody and Au/CaCO3 Synthesized Using Waste Eggshells for Ultrasensitive Detection of Ochratoxin A.

A novel ultrasensitive electrochemiluminescence (ECL) immunoassay based on Au/CaCO3 was proposed for detecting ochratoxin A (OTA) in coffee. Au/CaCO3 nanocomposites synthesized using waste eggshells as the template with a large surface area and excellent electrochemical properties were applied for immobilizing a large amount of Ru(bpy)3 2+ and conjugating a high-affinity nanobody (prepared by the phage display technique). Coupling of the Au/CaCO3 nanocomposites and nanobody technologies provided an ultrasensitive and highly selective ECL immunosensor for OTA detection in the range of 10 pg/mL-100 ng/mL with a low detection limit of 5.7 pg/mL. Moreover, the as-prepared ECL immunosensor showed excellent performance and high stability. Finally, the proposed ECL sensor was applied to analyze OTA in coffee samples, confirming the desirable accuracy and practical applicability potential. Overall, this work presents a new nanomaterial for fabricating the sensing interface of immunosensors by harnessing natural waste as the source and a method for detecting toxic OTA in foods.

Transition-metal-free and base promoted C-C bond formation via C-N bond cleavage of organoammonium salts.

A transition-metal-free and base promoted C-C bond forming reaction of benzyl C(sp3)-H bond with organoammonium salts via C-N bond cleavage has been reported. Benzyl ammonium salts as well as cinnamyl ammonium salt could couple readily with various benzyl C(sp3)-H species, producing the corresponding products in moderate to excellent yields with good functional group tolerance. Late stage chemical manipulation enabled the specific 1,2-diarylethane structure of products transformed into useful olefin compounds via dehydrogenation, which further demonstrated the utility of this reaction.

Palladium-Catalyzed Stereoselective Difunctionalization of Bicyclic Alkenes with Organoammonium Salts and Organoboronic Compounds.

A palladium-catalyzed difunctionalization of bicyclic alkenes with organoammonium salts and organoboronic compounds was reported. A wide range of functionalized cyclic products, including those bearing functional groups, were produced stereoselectively in good to excellent yields. The gram-scale experiment, one-pot operation, and synthetic application of ß-borylated products further demonstrated the synthetic value of this new reaction in organic synthesis.

Trifluoromethylation of Benzoic Acids: An Access to Aryl Trifluoromethyl Ketones.

The trifluoromethylation of benzoic acids with TMSCF3 was achieved through nucleophilic substitution with the use of anhydrides as an in situ activating reagent. Under the reaction conditions, a wide range of carboxylic acids including the bioactive ones worked well, thus providing a facile and efficient method for preparing aryl trifluoromethyl ketones from the readily available starting materials.

Practical Electro-Oxidative Sulfonylation of Phenols with Sodium Arenesulfinates Generating Arylsulfonate Esters.

A practical and sustainable synthesis of arylsulfonate esters has been developed through electro-oxidation. This reaction employed the stable and readily available phenols and sodium arenesulfinates as the starting materials and took place under mild reaction conditions without additional oxidants. A wide range of arylsulfonate esters including those bearing functional groups were produced in good to excellent yields. This reaction could also be conducted at a gram scale without a decrease of reaction efficiency. Those results well demonstrated the potential synthetic value of this reaction in organic synthesis.

Palladium-Catalyzed Decarbonylative Sonogashira Coupling of Terminal Alkynes with Carboxylic Acids.

A direct decarbonylative Sonogashira coupling of terminal alkynes with carboxylic acids was achieved through palladium catalysis. This reaction did not use overstoichiometric oxidants, thus overcoming the homocoupling issue of terminal alkynes. Under the reaction conditions, a wide range of carboxylic acids including those bioactive ones could couple readily with various terminal alkynes, thus providing a relative general method for preparing internal alkynes.

Transition-Metal-Free and Base-Promoted Carbon-Heteroatom Bond Formation via C-N Cleavage of Benzyl Ammonium Salts.

A facile and general method for constructing carbon-heteroatom (C-P, C-O, C-S, and C-N) bonds via C-N cleavage of benzyl ammonium salts under transition-metal-free conditions was reported. The combination of t-BuOK and 18-crown-6 enabled a wide range of substituted benzyl ammonium salts to couple readily with different kinds of heteroatom nucleophiles, i.e. hydrogen phosphoryl compounds, alcohols, thiols, and amines. Good functional group tolerance was demonstrated. The scale-up reaction and one-pot synthesis were also successfully performed.

Waste eggshell membrane-templated synthesis of functional Cu2+-Cu+/biochar for an ultrasensitive electrochemical enzyme-free glucose sensor.

A fast and sensitive test of blood glucose levels is very important for monitoring and reducing diabetic complications. Herein, a simple and sensitive non-enzymatic glucose sensing platform was fabricated by employing Cu2+-Cu+/biochar as the catalyst. The Cu2+-Cu+/biochar was synthesized through a bio-inspired synthesis, in which waste eggshell membrane (ESM) was introduced as a template to absorb Cu2+, then converting it into Cu2+-Cu+ biochar via a rapid pyrolysis. The structure and properties of the as-prepared Cu2+-Cu+ biochar were determined by scanning electron microscopy (SEM), FT-IR spectroscopy, Raman spectroscopy and cyclic voltammetry (CV). Due to great advantages of Cu2+-Cu+/biochar, such as high electrical conductivity, unique three-dimensional porous network and large electrochemically active surface area, the as-prepared Cu2+-Cu+ biochar modified electrode showed high catalytic activity towards glucose oxidization. The fabricated enzyme-free glucose sensor showed excellent performance for glucose determination with a linear range of 12.5-670 µM, and a limit of detection (LOD) of 1.04 µM. Moreover, the as-fabricated sensor has good anti-interference ability and stability. Finally, the proposed senor has been successfully applied to detect glucose in clinical samples (human serum). Owing to the green synthesis method, using biowaste ESM as a template, and the superior catalytic performance and low cost of Cu2+-Cu+/biochar, the developed sensor shows great potential in clinical applications for direct sensing of glucose.