Palladium-Catalyzed Heck/Suzuki Tandem Reaction of (Z)-1-Iodo-1,6-dienes and Organoboronic Acids.

The Heck/Suzuki tandem reaction has emerged as an essential strategy for the synthesis of complex molecules. Herein, an efficient palladium-catalyzed Heck/Suzuki tandem reaction of (Z)-1-iodo-1,6-dienes with organoboronic acids is described, providing various tetrahydropyridines in good to excellent yields under mild reaction conditions. The key to the success of this approach is the avoidance of the intramolecular second Heck insertion occurring prior to the transmetalation step. In addition, the asymmetric version of this reaction is investigated to deliver chiral tetrahydropyridine in excellent yield with promising enantioselectivity.

Pd(0)-Catalyzed Asymmetric Intramolecular Grignard-Type Reaction of Vinyl Iodide-Carbonyl.

The insertion of carbonyl into C(sp2)-Pd(II) σ-bond (Grignard-type addition) was not established until the 1990s. While this elemental reaction has been well explored since then, its application in Pd(0) asymmetric catalysis remain elusive. Herein, we report the Pd(0)-catalyzed asymmetric intramolecular Grignard-type reaction of vinyl iodide-carbonyl in the presence of HCO2H additive, affording cyclic allylic alcohol with good to excellent enantioselectivity and diastereoselectivity. Mechanistic studies suggested that besides serving as an efficient reductant, HCO2H is also capable of facilitating protonation of the involved secondary alkoxyl-Pd(II), thus completely suppressing the ß-H elimination. Moreover, no KIE was found in the competing reaction between vinyl iodide-aldehyde and 1-deuterated one, demonstrating the facile step of aldehyde insertion.

(3+2) Annulation of 4-Acetoxy Allenoate with Aldimine Enabled by AgF-Assisted P(III)/P(V) Catalysis.

A phosphine-catalyzed (3+2) annulation of 4-acetoxy allenoate and aldimine with the assistance of AgF is described. The success of this reaction hinges on the metathesis between the enolate-phosphonium zwitterion and AgF, leading to a key intermediate comprising of silver enolate and a fluorophosphorane P(V)-moiety. The former is able to undergo a Mannich reaction with aldimine, whereas the latter initiates a cascade sequence of AcO-elimination/aza-addition, thus furnishing the P(III)/P(V) catalysis. By taking advantage of the silver enolate, a preliminary attempt at an asymmetric variant was conducted with the combination of an achiral phosphine catalyst and a chiral bis(oxazolinyl)pyridine ligand (PyBox), giving moderate enantioselectivity.

Access to Cyclopentenone via Pd(0)-Catalyzed Reductive Cyclization of (Z)-5-Iodo-4-pentenenitrile.

A ligand-free Pd(0)-catalyzed cyclization of (Z)-5-iodo-4-pentenenitrile has been realized with the help of HCO2H reductant, which is followed by imine hydrolysis to afford cyclopentenone derivatives in moderate to good yields. Control experiments clearly points out that the proton originally came from HCO2H plays a crucial role on protonation of the resultant imido-Pd2+ intermediate. This protocol features mild condition, operational simplicity, as well as wide functional group tolerance.

Nanoengineering of electrodes via infiltration: an opportunity for developing large-area solid oxide fuel cells with high power density.

Although nanoengineering of electrodes opens up the way to the development of solid oxide fuel cells (SOFCs) with improved performance, the practical implementation of such advances in cells suitable for widespread use remains a challenge. Here, the demonstration of large-area, commercially relevant SOFCs with two nanoengineered electrodes that display excellent performance is reported. The self-assembled nanocomposite La0.6Sr0.4CoO3-δ and Co3O4 is strategically designed and deposited into the well-interconnected Ce0.9Gd0.1O2-δ backbone as a cathode to enable an ultra-large electrochemically active region. The nanometer-scale Ce0.8Gd0.2O2-δ is deposited into a conventional Ni/yttria-stabilized zirconia (YSZ) anode to provide more active oxygen exchange kinetics and electronic conductivity compared to YSZ. The resulting nanoengineered cell with an effective size of 4 cm × 4 cm delivers a remarkable power output of 19.2 W per single cell at 0.6 V and 750 °C. These advancements have potential to facilitate the future development of high-performance SOFCs at a large scale by nanoengineering of electrodes and are expected to pave the way for the commercialization of this technology.

Effect of tea polyphenols on the physicochemical, structural and digestive properties of modified high amylose corn starch.

In this study, starch-polyphenol complexes (CES-TPS complexes) were prepared using various ratios (0%, 2%, 4%, 6%, 8%, and 10%, based on starch) of tea polyphenols (TPS) and high amylose corn starch (HACS) pretreated with starch branching enzyme (SBE). It was aimed to determine the effects of TPS on the physicochemical and structural properties and digestibility of the CES-TPS complexes. Scanning electron microscopy and laser particle size analysis showed that the addition of a moderate amount of TPS will reinforce interaction force, while excessive TPS will cause a loose structural morphology, leading to an increase in starch particle size. Thermal property analysis indicated that SBE pre-treatment decreased TO, TP and TC of HACS, and the gelatinization temperature was further reduced after adding TPS. The digestion of CES-TPS complexes was investigated using an Artificial Gut analyzer; the predicted glycemic index of starch samples decreased with the addition of a low concentration of TPS (2-6%), while there was a significant increment in the pGI of starch samples when a high concentration of TPS (8-10%) was added. XRD analysis showed that the relative crystallinity of the CES-TPS complexes further increased to 21.91% and then decreased to 19.38% with the increase of TPS concentration. The ratios of 1047/1022 cm-1 presented the opposite trend to that determined by FT-IR.

Domino Sequences Involving Stereoselective Hydrazone-Type Heck Reaction and Denitrogenative [1,5]-Sigmatropic Rearrangement.

Although the Heck reactions of alkene partners with various electrophiles have achieved great success, the variant focused on carbon═heteroatom counterparts still remains elusive. Herein, we report a Pd(0)-catalyzed asymmetric intramolecular hydrazone-type Heck reaction of N-[(Z)-3-iodoallyl]-aminoacetaldehyde and hydrazine hydrate (NH2NH2-H2O), wherein the required hydrazone is in situ generated via an acid-promoted condensation. A key strategic advantage of this Heck paradigm is that the resultant Heck product allylic diazene rapidly undergoes stereospecific denitrogenative [1,5]-sigmatropic rearrangement, eventually furnishing a domino sequence toward 3-substituted tetrahydropyridine (THP) with high enantioselectivity. The substrate-induced diastereoselective version has also been realized, exclusively giving cis-2,5-disubstituted THPs. The utility of this sequence is demonstrated by the formal synthesis of multiple valuable bioactive targets, including 3-ethylindoloquinolizine, preclamol, and niraparib.

Pd(0)-Catalyzed Asymmetric 7-Endo Hydroacyloxylative Cyclization of 1,6-Enyne Enabled by an Anion Ligand-Directed Strategy.

Despite diversity in reaction mechanisms, the palladium-catalyzed cyclization of 1,6-enyne generally proceeds in a 5-exo manner. Herein, we report the development of a Pd(0)-catalyzed hydroacyloxylative cyclization of 1,6-enyne in either 7-endo-trig or 6-exo-trig fashion when paired with an appropriate dihaloacetic acid reactant, such as F2HCCO2H and Cl2HCCO2H. Using the combination of Pd2(dba)3 and a chiral phosphine ligand, the hydroacyloxylative cyclization of 1,6-enyne bearing a 1,1-disubstituted alkene moiety readily gives highly enantiopure seven-membered heterocycles while the reaction of those having a 1,2-disubstituted alkene affords six-membered rings with moderate enantioselectivity. Preliminary experimental studies suggest a reaction mechanism featuring an unusual E-to-Z vinyl-Pd(II) isomerization and alkene trans-oxypalladation, which is proven to be governed by the rationally selected carboxylate.

The expression profile of 79 genes from 107 viruses revealed new insights into disease susceptibility in rats, mice, and muskrats.

The coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread over the world, resulting in a global severe pneumonia pandemic. Both the cell receptor angiotensin-converting enzyme 2 (ACE2) and the breakdown of S protein by transmembrane serine protease 2 (TMPRSS2) are required by SARS-CoV-2 to enter the host cells. Similarly, the expression level of viral receptor genes in various organs determines the likelihood of viral infection. Several animal species have been found to be infected by the SARS-CoV-2, such as minks, posing an enormous threat to humans. Because the mice and rats were closely related to human and the fact that rats and mice have a risk of infection by SARS-CoV-2 with specific variants, we investigated the expression patterns of 79 receptor genes from 107 viruses, including SARS-CoV-2, in 14 organs of the rat and mouse, and 5 organs of the muskrat, to find the most likely host organs to become infected with certain viruses. The findings of this study are anticipated to aid in prevention of zoonotic infections spread by rats, mice, muskrats, and other rodents.

Pd0 -Catalyzed Asymmetric Carbonitratation Reaction Featuring an H-Bonding-Driven Alkyl-PdII -ONO2 Reductive Elimination.

Reductive elimination of alkyl-PdII -O is a synthetically useful yet underdeveloped elementary reaction. Here we report that the combination of an H-bonding donor [PyH][BF4 ] and AgNO3 additive under toluene/H2 O biphasic system can enable such elementary step to form alkyl nitrate. This results in the Pd0 -catalyzed asymmetric carbonitratations of (Z)-1-iodo-1,6-dienes with (R)-BINAP as the chiral ligand, affording alkyl nitrates up to 96 % ee. Mechanistic studies disclose that the reaction consists of oxidative addition of Pd0 catalyst to vinyl iodide, anion ligand exchange between I- and NO3 - , alkene insertion and SN 2-type alkyl-PdII -ONO2 reductive elimination. Evidences suggest that H-bonding interaction of PyH⋅⋅⋅ONO2 can facilitate dissociation of O2 NO- ligand from the alkyl-PdII -ONO2 species, thus enabling the challenging alkyl-PdII -ONO2 reductive elimination to be feasible.

Effect of different starch acetates on the quality characteristics of frozen cooked noodles.

The physicochemical properties of starch acetates with an equal degree of substitution prepared from pea, corn, and wheat starch and their effects on frozen cooked noodle (FCN) quality were investigated. The result showed that the three kinds of starch acetates had different effects on the quality of FCN due to their different blue values, freeze-thaw stability, and crystalline morphology analyzed by XRD (p < .05). The FCN with the addition of 20% CAS exhibited slow deterioration of textural properties during holding for 30 min. The analysis of the changes in the content of free SH group and glutenin macropolymer (GMP) demonstrated that the addition of CAS promoted protein disulfide cross-linking and decreased protein mobility during holding. Fourier transform infrared spectroscopy (FT-IR) revealed that FCN with the addition of CAS had low decrement in α-helix and ß-sheet during holding, indicating that starch acetates contributed to the maintenance of the gluten network structure.

Pd(0)-Catalyzed Intramolecular Reductive Heck Reaction of Vinyl Iodide and Oxime Ether: Enantioselective Synthesis of Cyclic Allylic N-Alkoxy Amine.

Whereas the intramolecular reductive Heck reaction of aryl/vinyl halide and alkene has been well documented, the oxime analogue remains extremely elusive. Herein we report the Pd(0)-catalyzed intramolecular reductive Heck reaction of vinyl iodide and oxime ether with the use of formic acid as the reductant. It is found that the TsOH additive plays a crucial role in the reaction efficiency, and the (S)-SEGPhos ligand enables cyclic allylic N-alkoxy amine products with high enantioselectivity.

Synthesis of trisubstituted hydrazine via MnO2-promoted oxidative coupling of N,N-disubstituted hydrazine and boronic ester.

A MnO2-promoted oxidative coupling process between N,N-disubstituted hydrazine and boronic ester is reported. A 1,1-diazene species is firstly generated upon oxidation of a hydrazine substrate in the presence of MnO2 which then interacts with boronic ester to form the key intermediate boron-ate complex, followed by migration from boron to nitrogen to form a new C-N bond. This new finding provides mild, scalable, and operationally straightforward access to trisubstituted hydrazine.

Physicochemical and digestive properties of A- and B-type granules isolated from wheat starch as affected by microwave-ultrasound and toughening treatment.

In this study, the effect of microwave-ultrasound or/and toughening treatment on the physicochemical, structural properties, and in vitro digestibility of A- and B-type granules isolated from wheat starch were investigated. From the SEM, microwave-ultrasound and toughening treatment (MU-T) led to the appearance of irregular and disrupted structure significantly and an increment in the resistant starch content of A- and B-type granule. Furthermore, the MU-T starch possessed the lowest swelling power, light transmittance, and gelatinization temperature range (Tc -To) and the highest ΔH. After MU-T, the relative crystallinity (RC) of X-ray pattern, Fourier transform infrared ratio of 1047/1022 cm-1, and the content of double helix and single helix of 13C CP/MAS NMR had increased significantly. In particular, there was a difference in the content of RS and SDS between A-starch granules and B-starch granules as well as their changes after modification (from 69.305% to 82.93 for A-starch and form 74.97% to 88.17 for B-starch, respectively), which was a similar trend with RC and helix content. This study indicated that, for both A-type granule and B-type granule starches, microwave-ultrasound and toughening treated samples had unique properties compared to singly modified starches.

PhI(OAc)2-Mediated Dihalogenative Cyclization of 1,6-Enyne with Lithium Halide.

The dihalogenative cyclization of 1,6-enyne with the assistance of PhI(OAc)2 and lithium halide is presented. A plausible radical mechanism is proposed, which consists of addition of halogen radical to alkene, 5-exo-dig radical cyclization of enyne and halogenation via radical coupling. The alkenyl- and alkyl-halide groups in the resulted pyrrolidine products have been demonstrated to be facile handles for further transformations.

Phosphine-catalysed (4+1) annulations of ß'-acetoxy allenoate with ß,γ-unsaturated carbonyl compounds.

While ß,γ-unsaturated carbonyl compounds have been widely used as γC- or αC-nucleophiles, their potential αC,αC-bisnucleophilic reactivity is still underdeveloped. Herein, a phosphine-catalysed (4+1) annulation of ß'-acetoxy allenoate and a ß,γ-unsaturated carbonyl compound is reported, wherein ß'-acetoxy allenoate is the 1,4-biselectrophilic component while the ß,γ-unsaturated carbonyl compound serves as an αC,αC-bisnucleophile. The process not only provides a new reaction mode of ß,γ-unsaturated carbonyl compounds under mild conditions but also broadens the scope of Lewis base-catalysed annulation of acetoxy allenoate.

Pd(0)-Catalyzed Asymmetric Carbohalogenation: H-Bonding-Driven C(sp3)-Halogen Reductive Elimination under Mild Conditions.

Carbon-halogen reductive elimination is a conceptually novel elementary reaction. Its emergence broadens the horizons of transition-metal catalysis and provides new access to organohalides of versatile synthetic value. However, as the reverse process of facile oxidative addition of Pd(0) to organohalide, carbon-halogen reductive elimination remains elusive and practically difficult. Overcoming the thermodynamic disfavor inherent to such an elementary reaction is frustrated by the high reaction temperature and requirement of distinctive ligands. Here, we report a general strategy that employs [Et3NH]+[BF4]- as an H-bond donor under a toluene/water/(CH2OH)2 biphasic system to efficiently promote C(sp3)-halogen reductive elimination at low temperature. This enables a series of Pd(0)-catalyzed carbohalogenation reactions, including more challenging and unprecedented asymmetric carbobromination with a high level of efficiency and enantioselectivity by using readily available ligands. Mechanistic studies suggest that [Et3NH]+[BF4]- can facilitate the heterolytic dissociation of halogen-PdIIC(sp3) bonds via a potential H-bonding interaction to reduce the energy barrier of C(sp3)-halogen reductive elimination, thereby rendering it feasible in an SN2 manner.

Untargeted metabolomics revealed therapeutic mechanisms of icariin on low bone mineral density in older caged laying hens.

Osteoporosis is a common chronic disease in the elderly population and in some domestic animals. Caged layer osteoporosis (CLO) is a common bone metabolism disease that was recently recommended as an ideal animal model for osteoporosis. This study aimed to investigate the therapeutic effect and mechanism of dietary icariin (ICA), the main bioactive component of the Chinese herb Epimedium, on low bone mineral density (BMD) in older caged laying hens. A total of 216, 54-week-old Lohmann pink-shell laying hens were allocated to three groups, comprising one control group and two treatment groups that were additionally supplied with 0.5 or 2.0 g kg-1 ICA. The results showed that dietary ICA significantly increased the femur BMD by 49.3% and the tibia BMD by 38.9%, improved the microstructure of bone tissue, decreased levels of the bone metabolism index, enhanced serum antioxidant capacity and regulated messenger RNA expression of bone-related genes. ICA-induced differential metabolites were clarified by using untargeted metabolomics assays. Furthermore, correlation analysis between differential metabolites and BMD indicated that eight differential metabolites correlated highly with both femur and tibia BMD, including uridine, taurine, palmitic acid, adrenic acid, fexofenadine, lysoPC(18 : 1), lysoPE(20 : 3/0 : 0) and 3-acetyl-11-keto-beta-boswellic acid. ICA mainly perturbed pyrimidine metabolism, taurine metabolism and lipid metabolism, which led to increased BMD in older caged laying hens. These findings revealed underlying therapeutic mechanisms of dietary ICA on low BMD, and provided reference metabolites for the early diagnosis of osteoporosis.

Pd(0)-Catalyzed Cyclizative Carboboration of n-Iodo-1,6-diene (n = 1 or 2): Access to Structurally Complex Allylboronates and Alkylboronates.

A Pd(0)-catalyzed cyclizative carboboration reaction of n-iodo-1,6-diene (n = 1, 2) with B2pin2 has been developed. When 1-iodo-1,6-diene was employed as the substrate, a process of intramolecular 6,6-alkenylboration was achieved to deliver 6-membered cyclic allylborate. On the other hand, 2-iodo-1,6-diene was found to proceed via 2-cyclopropanation/1-boration, thus affording a (bicyclo[3.1.0]hexan-1-ylmethyl)borate product.

Access to Aryl-Naphthaquinone Atropisomers by Phosphine-Catalyzed Atroposelective (4+2) Annulations of δ-Acetoxy Allenoates with 2-Hydroxyquinone Derivatives.

Although asymmetric phosphine catalysis is a powerful tool for the construction of various chiral carbon centers, its synthetic potential toward an enantioenriched atropisomer has not been explored yet. Reported herein is a phosphine-catalyzed atroposelective (4+2) annulation of δ-acetoxy allenoates and 2-hydroxyquinone derivatives. The reaction provides expedient access to aryl-naphthaquinone atropisomers by the de novo construction of a benzene ring. The two functionalities of the catalyst, a tertiary phosphine (Lewis base) and a tertiary amine (Brønsted base), cooperatively enable this process with high regio- and enantioselectivities.