Chemo-, regio- and stereoselective access to polysubstituted 1,3-dienes via Nickel-catalyzed four-component reactions.

1,2-Difunctionalization of alkynes offers a straightforward approach to access polysubstituted alkenes. However, simultaneous multi-component cascade transformations including difunctionalization of two alkynes with both syn- and anti-selectivity in one catalyst system is undeveloped and proves to be a significant challenge. Herein, we report a Nickel-catalyzed four-component reaction to access polysubstituted 1,3-dienes using two terminal alkynes, aryl boroxines, and perfluoroalkyl iodides, wherein the reaction forms three new C-C bonds in a single vessel and serve as a modular strategy to access polysubstituted 1,3-dienes with excellent chemoselectivity, good regioselectivity and exclusive stereoselectivity. Control experiments reveal the plausible reaction mechanism and DFT calculations explain the cause for the formation of this unusual four-component reaction. Furthermore, we successfully incorporate two biologically active units into 1,2,3,4-tetrasubstituted 1,3-dienes, which greatly increases the diversity of molecular scaffolds and brings more potential values to medicinal chemistry, the synthetic utility of our protocol is further demonstrated by the late-stage transformations.

Highly Stereoselective Synthesis of Multisubstituted Olefins from Alkynyl Tetracoordinate Borons and Iodonium Ylides via a Cyclic Intermediate.

We developed an intriguing and practical strategy for highly stereoselective assembly of multisubstituted olefins from alkynyl tetracoordinate boron species via a cyclic intermediate with 1,2-phenyl migration. We also developed a general method for the construction of deuterated trisubstituted alkenes from a cheap deuteration source, D2O, and the corresponding deuterated trisubstituted alkenes were obtained with excellent deuteration rates. This transformation features a novel reaction mechanism, exclusive stereoselectivity, and deuterated trisubstituted alkenes with excellent deuteration ratios.

1,1-Oxycarbonation of Terminal Alkynes via Sequential Borylation, 1,2-Migration, and Oxidation with Oxone.

Alkynes are readily available and multifunctional synthetic intermediates, but their 1,1-oxofunctionalization remains challenging. Herein, we report a 1,1-oxycarbonation of terminal alkynes to construct ketones through sequential borylation, 1,2-carbon migration, and oxidation with Oxone as the proton source and oxidant. The synthetic potential of this transformation is showcased by the broad functional groups, scale-up synthesis, and diverse product transformations.

Ni-catalysed assembly of axially chiral alkenes from alkynyl tetracoordinate borons via 1,3-metallate shift.

Asymmetric synthesis based on a metallate shift of tetracoordinate borons is an intriguing and challenging topic. Despite the construction of central chirality from tetracoordinate boron species via a 1,2-metallate shift, catalytic asymmetric synthesis of axially chiral compounds from such boron 'ate' complexes is an ongoing challenge. Axially chiral alkenes have received great attention due to their unique characteristics and intriguing molecular scaffolds. Here we report an enantioselective nickel-catalysed strategy for the construction of axially chiral alkenes via a 1,3-metallate shift of alkynyl tetracoordinate boron species. The chemoselectivity, regioselectivity and atroposelectivity can be regulated and well-controlled from readily accessible starting materials with a cheap transition-metal catalyst. Downstream transformations indicate the powerful conversion ability of such compounds in this protocol, and late-stage elaborations of bioactive compounds can also be achieved. Mechanistic experiments reveal that regioselective syn-addition of an aryl-Ni complex with a carbon-carbon triple bond and subsequent 1,3-phenyl migration are the two key steps for the synthesis of axially chiral alkenes.

[Post-stroke dysphagia treated with four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy on post-stroke dysphagia treated with four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation. METHODS: Sixty patients with post-stroke dysphagia were randomly divided into an observation group and a control group, with 30 cases in each group. The neuromuscular electrical stimulation was adopted in the control group. Besides the treatment as the control group, in the observation group, the four-step acupuncture therapy for opening orifices and benefiting throat was supplemented. Step 1: the three areas of scalp acupuncture on the affected side were stimulated. Step 2: pricking method was operated on the posterior pharyngeal wall. Step 3: bleeding technique was operated at Jinjin (EX-HN 12) and Yuye (EX-HN 13). Step 4: deep insertion of needle was operated at three-pharynx points. The needles were retained for 30 min at the three areas of scalp acupuncture and the three-pharynx points. The intervention of each group was delivered once daily, 6 times a week, at the interval of 1 day. One course of treatment was 1 week and 4 successive courses were required. The rating of Kubota water swallow test, the score of standardized swallowing assessment (SSA) and the rating of Rosenbek penetration- aspiration scale (PAS) were observed before and after treatment in patients of the two groups. The incidence of clinical complications and clinical efficacy were compared between the two groups. RESULTS: Compared with those before treatment, the rating of Kubota water swallow test, the scores of SSA and the rating of PAS of patients in the two groups were decreased after treatment (P<0.01), and the values of the observation group were lower than those of the control group after treatment (P<0.05). The incidence of clinical complications in the observation group was 13.3% (4/30), lower than 36.7% (11/30) in the control group (P<0.05). The total effective rate in the observation group was 93.3% (28/30), which was better than 70.0% (21/30) in the control group (P<0.05). CONCLUSION: The four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation can improve the swallowing function of patients with post-stroke dysphagia and reduce the incidence of clinical complications.

Divergent Synthesis of 1,1-Carbonyl Amino Alkyl Borons from Indoles.

α-Boryl carbonyl species and α-boryl amino compounds are valuable and important frameworks in organic synthesis. However, the strategies that could merge the two scaffolds into one compound, named 1,1-carbonyl amino alkyl boron, are elusive and underdeveloped. Herein, we present an efficient method that could address this gap and produce 1,1-carbonyl amino alkyl borons from readily accessible indoles via oxidation by m-CPBA or oxone. This reaction features operational simplicity, divergent synthesis, broad substrate scope, and valuable products.

Arylation of Terminal Alkynes: Transition-Metal-Free Sonogashira-Type Coupling for the Construction of C(sp)-C(sp2) Bonds.

Alkynes are attractive synthons for organic chemistry. Despite the prevalence of transition-metal-catalyzed Sonogashira reactions, a transition-metal-free version of the arylation of terminal alkynes is elusive. Herein, we report an efficient transition-metal-free Sonogashira-type coupling reaction for the one-pot arylation of alkynes to construct C(sp)-C(sp2) bonds from a tetracoordinate boron intermediate with NIS as a mediator. With its high efficiency, wide substrate range, and good functional group tolerance, this method is further supported by the gram-scale synthesis and subsequent modification of complex molecules.

Difluorocarbene-Enabled Synthesis of 3-Alkenyl-2-oxindoles from ortho-Aminophenylacetylenes.

Herein, we report a transition-metal-free [4 + 1] cyclization pathway from difluorocarbene and ortho-amino aryl alkynone, rendering an effective and universal strategy for the construction of 3-alkenyl-2-oxindoles. Our strategy starts from cheap and accessible ortho-amino aryl alkynone instead of the direct indole skeleton; moreover, in situ generated difluorocarbene from commercially available halogenated difluoroalkylative reagents enables the cleavage of a C-N bond and formation of new C-N bonds and C-C bonds.

Unconventional Transformations of Difluorocarbene with Amines and Ethers.

ConspectusFluorine-containing compounds are extensively involved in various fields originating from intriguing and unique characteristics of fluorine atom; notably, in pharmaceuticals, the involvement of a fluorine atom or a fluorine-containing group is a chief technique for improving the pesticide effect and developing new drugs. Difluorocarbene, one of the most important and powerful fluorine-containing reagents, is widely employed and studied in many areas mainly to assemble gem-difluoromethyl molecules, including but not limited to the abundant reactions between difluorocarbene with nucleophilic substrates, Wittig reaction with ketones or aldehydes, cascade reaction with both a nucleophile and an electrophile, or [2+1] cycloaddition with alkenes or alkynes. However, its unconventional and intriguing protocols beyond as a difluoromethyl synthon have rarely been studied, and thus, it is highly desired given its abundance, inexpensiveness and peculiar properties. In this Account, we mainly discuss our discovery with unconventional transformations of difluorocarbene, instead of as a sole difluoromethyl source (different from other dihalocarbene), actually can serve as an electron acceptor to activate C-X bonds (X = N and O) and thus promote a myriad of fascinating transformations for the assembly of versatile valuable products with various aza-compounds (primary/secondary/tertiary amines as well as NH3 and NaNH2 and so on) and aliphatic ethers in the absence of transition metals and expensive ligands. Inspired by the electron-deficient characteristics of difluorocarbene, we first found that the isocyanides could be readily formed in situ when the unoccupied orbital of difluorocarbene meets the lone-pair of primary amines; in basic condition, a cascade defluorination and cyclizations could afford plethora of valuable N-containing heterocycles. Meanwhile, we disclosed that cyano anion could be accessible in situ as well when difluorocarbene and NaNH2 or NH3 were mixed up in suitable basic conditions, and thus a series of aryl nitrile compounds were obtained in the presence of Pd catalysis and ArI. Interestingly, when difluorocarbene encountered secondary amines, formamides were rendered under mild reactions. Of note, concomitant functionalizations of C and N moieties via cleavage of the unstrained C(sp3)-N bond in the absence of metal and oxidant are sparce, which indeed significantly add versatility and diversity to products. Gratifyingly, by uitilizing difluorocarbene and cyclic tertiary amines, we achieved difluorocarbene-mediated deconstructive functionalizations for the first time, showing successive C(sp3)-N bond scission of amines and simultaneous functionalization of C and N atoms which would be introduced into the products in the absence of transition metals and oxidants. This method provides a brand-new while very universal synthetic pathway to selectively cleave inert unactivated Csp3-N bonds, in which halodifluoromethyl reagents act as both C1 synthon and halo (Cl, Br, I) sources. Fascinatingly, nitrogen ylides are generated in situ from difluorocarbene and tertiary amines, and an intriguing and universal approach for deaminative arylation or alkenylation of tertiary amines was disclosed for the first time in appropriate basic conditions, which represents an intriguing reaction mode to lead to a formal transition-metal free Suzuki cross coupling. Besides, we also disclosed that difluorocarbene could proceed novel atom recombination to render meaningful 2-fluoroindoles or 3-(2,2-difluoroethyl)-2-fluoroindoles from ortho-vinylanilines, 3-fluorined oxindoles from 2-aminoarylketones, in which difluorocarbene acts as a C1 synthon and F1 source simultaneously. Last but not the least, we recently found that the lone-pair-electron of oxygen could trap difluorocarbene as well to form oxonium ylide, which eventually leads to C-O bond cleavage with the formation of difluoromethyl ethers.

A Cohort Study of Surgical Indexes, Postoperative Complications, Recovery Speed, and Prognosis of Stanford Type A Aortic Dissection Compared with Traditional Sun's Operation.

Objective: The objective is to explore the surgical index, postoperative complications, recovery speed, and prognosis of Stanford type A aortic dissection (AD) compared with traditional 'Sun's operation. Methods: One hundred patients with Stanford type A AD treated from February 2018 to February 2021 were enrolled in our hospital. Patients were randomly divided into control and research group. The former group underwent traditional Sun's surgery, and the latter group underwent combined debranching surgery. The general data, surgical indexes, total amount of blood transfusion, renal function 72 hours after operation, postoperative indexes during hospitalization, and follow-up results after discharge were compared between the two groups. Results: The CPB time, ACC time, operation time, and postoperative total drainage volume of the study group were all lower than those of the control group, and the intraoperative urine volume of the study group was higher than that of the control group (P < 0.05). The total amount of RBC infused in the study group was higher than that in the control group, while the total amount of PLT, cryoprecipitate, and plasma infusion in the study group was lower than that in the control group (P < 0.05). At 72 hours after operation, BUN, Scr, and UA in the study group were significantly lower than those in the control group (P < 0.05). The number of the secondary intubation, hemodialysis, neurological complications, and deaths in the study group was significantly lower than that in the control group (P < 0.05). Conclusion: Both Sun's operation and branch removal are more effective treatment methods, and the two different surgical methods have different indications, advantages, and disadvantages, so different surgical methods can be chosen according to different conditions for Stanford AD. The possible postoperative complications should be comprehensively analyzed in the clinical work in order to reduce the occurrence of postoperative complications and improve the cure rate.

Comparison of Root Ecological Stoichiometry between Non-Growing Season and Growing Season of Grassland on the Chang Tang Plateau.

Root C: N: P stoichiometry affect the geochemical cycles of ecosystems, while a few studies were conducted on it and its relationship with soil nutrients, especially in the non-growing season. In this study, we investigated the root C:N:P stoichiometry of alpine steppe(AS), alpine meadow steppe(AMS), and alpine meadow(AM) in April (non-growing season) and August(growing season) in 2013. The results showed that: (1) There were no differences in root C, N, P, C: N, C:P, and N:P with a depth of AS in April. However, root C and C: N increased with depth, while N and N:P decreased with a depth of AS in August. In both months, the variation of root C, N, P, C: N with depth in AM was consistent with that of AS in August, and root C at deep layer decreased in August, which indicated roots of AM began to grow in April No significant difference of root C, N, C: N and N:P with depth was found, while P and C:P varied between the two months of AMS. Root P content at 20-30 cm was higher than that of other soil layers in April, which was significantly higher than that of AS, while no significant difference was found in August. (2) Grassland types had significant effects on soil nutrients (except TP) at 0-10 cm and 20-30 cm soil layers. (3) No significant correlation between soil nutrients and root C, N, P, C: N, C: P, and N: P was found in April. Soil TN and AN content had a significant positive correlation with root N: P, indicating that soil nitrogen was the primary N source of the root. Soil TP and AP were significantly negatively correlated with root C and C: N in August. This study can provide basic data and provide theoretical support for further understanding the role of grassland roots in nutrient cycling.

Cu-Catalyzed Three-Component Cascade Synthesis of 1,3-Benzothiazines from ortho-Aminohydrazones and Bromodifluoroacetamides.

An efficient and convenient synthesis of benzo[d][1,3]thiazine has been developed by employing a copper-catalyzed transformation of readily available ketone-derived hydrazones with elemental sulfur and bromodifluoroalkylative reagents. The strategy involves an S8-catalyzed selective triple-cleavage of bromodifluoroacetamides, which acts as a C1 synthon at the 2-position of benzo[d][1,3]thiazine. A mechanism proceeding through a Cu-carbene intermediate is proposed for the C-S bond formation.

Enantioselective Copper-Catalyzed sp2/sp3 Diborylation of 1-Chloro-1-Trifluoromethylalkenes.

Fluorine-containing organoboron compounds have emerged as novel building blocks in chemical synthesis; among them, fluorinated sp2/sp3 diborylated compounds are particularly appealing, since they might undergo chemoselective and diversified transformations of different C-B bonds with fluorinated functionality, thus bringing versatility and complexity to the eventual products. However, expedient, synthetic strategies for the construction of such fluorinated diborylative compounds are very sparse. Herein, we disclose enantioselective Cu-catalyzed sp2/sp3 diborylations of 1-chloro-1-trifluoromethylalkenes, leading to diborylated compounds bearing a gem-difluoroalkenyl moiety; most intriguingly, the new formed C-B bonds include one stereoselective and optically pure Csp3-B bond. Further transformations on the eventual products demonstrated the values of our presented strategy.

Acquisition pattern of nitrogen by microorganisms and plants affected by gravel mulch in a semiarid Tibetan grassland.

As an important coarse inorganic fraction of soil, gravel may regulate the effects of the interaction between above- and belowground communities and affect the relationship between microorganisms and plants in alpine ecosystems. However, comparatively little is known about the effects of gravel on the acquisition pattern of nitrogen (N) by microorganisms and plants in alpine ecosystems. In this study, a 15N-labelling experiment was conducted to investigate the acquisition pattern of organic (15N-glycine) and inorganic N (15N-NO3- and 15N-NH4+) by microorganisms and plants under three particle sizes of gravel mulch (fine: 2-10 mm, medium: 10-20 mm, coarse: 20-40 mm) on a semiarid Tibetan grassland. Gravel mulch significantly improved the 15N recovery of Stipa purpurea, but had no significant impacts on A. nanschanica. Therefore, gravel mulch decreased the ratio of microbial biomass 15N recovery to plant biomass 15N recovery for S. purpurea, but caused little effect on the state of N competition between plants and soil microbes for A. nanschanica. The N absorption preference of plants from both species shifted from an individual preference for 15N-NO3- in the natural (i.e., control) microplots to a common preference for 15N-NO3-and 15N-NH4+ in the fine- and medium-sized gravel mulch microplots, while there were no significant differences in microbial N recovery between 15N-NO3- and 15N-NH4+ across all treatments. The results helped to improve the understanding of the acquisition pattern of N by microorganisms and plants under the influence of gravel mulch in alpine ecosystems, and provide theoretical support for revegetation in alpine ecosystems in the future.

Recent Advances in the Construction of Fluorinated Organoboron Compounds.

Fluorinated organoboron compounds are important synthetic building blocks that combine the unique characteristics of a fluorinated motif with the versatile synthetic applications of organoboron moiety. This review article guides the research on fluorinated organoboron compounds mainly from four aspects in recent years: selective monodefluoroborylation of polyfluoroarenes and polyfluoroalkenes, selective borylation of fluorinated substrates, selective fluorination of organoboron compounds, and borofluorination of alkynes/olefins. In addition, this review will provide a necessary guidance and inspiration for the research on the valuable synthetic building block fluorinated organoboron compounds.

Solvent-Dependent Cyclization of 2-Alkynylanilines and ClCF2COONa for the Divergent Assembly of N-(Quinolin-2-yl)amides and Quinolin-2(1H)-ones.

Herein, we present an expedient Cu-catalyzed [5 + 1] cyclization of 2-alkynylanilines and ClCF2COONa to divergent construction of N-(quinolin-2-yl)amides and quinolin-2(1H)-ones by regulating the reaction solvents. Notably, nitrile acts as a solvent and performs the Ritter reactions. ClCF2COONa is used as a C1 synthon in this transformation, which also represents the first example for utilization of ClCF2COONa as an efficient desiliconization reagent. The current protocol involves in situ generation of isocyanide, copper-activated alkyne, Ritter reaction and protonation.

Flexible Capacitive Curvature Sensor with One-Time Calibration for Amphibious Gait Monitoring.

Wearable devices developed with flexible electronics have great potential applications for human health monitoring and motion sensing. Although material softness and structural flexibility provide a deformable human-machine interface to adapt to joint bending or tissue stretching/compression, flexible sensors are inconvenient in practical uses as they usually require calibration every time they are installed. This article presents an approach to design and fabricate a flexible curvature sensor to measure human articular movements for amphibious applications. This flexible sensor employs the capacitive sensing principle, where the dielectric layer and electrodes are made from the polyurethane resin and eutectic gallium-indium (EGaIn) liquid metal; and the fabrication process is implemented with shape deposition molding for batch production. The sensing method for articular rotation angles employs the Euler beam model to make the sensor reusable after one-time calibration by compensating for the unpredicted manual installation error. The illustrative application to ankle sensing in amphibious gaits shows that the root-mean-square error is within 5° for different walking speeds (0.7-1.1 m/s) in treadmill tests and the maximum error is within 3° for underwater sensing with quasi-static measurements. It is expected that the proposed waterproof flexible sensor can push the boundaries of wearable robotics, human locomotion, as well as their related applications.

Design, synthesis, and biological activity of novel semicarbazones as potent Ryanodine receptor1 inhibitors of Alzheimer's disease.

Ryanodine receptors (RyRs) are important ligand-gated Ca2+ channels; their excessive activation leads to Ca2+ leakage in the sarcoplasmic reticulum that may cause neurological diseases. In this study, three series of novel potent RyR1 inhibitors based on dantrolene and bearing semicarbazone and imidazolyl moieties were designed and synthesized, and their biological activity was evaluated. Using a single-cell calcium imaging method, the calcium overload inhibitory activities of 26 target compounds were tested in the R614C cell line, using dantrolene as a positive control. The preliminary investigation showed that compound 12a suppressed Ca2+ release as evidenced by store overload-induced Ca2+release (SOICR) (31.5 ± 0.1%, 77.2 ± 0.1%, 93.7 ± 0.2%) at 0.1 µM, 3 µM and 10 µM, respectively. Docking simulation results showed that compound 12a could bind at the active site of the RyR1 protein. The Morris water-maze test showed that compound 12a significantly improved the cognitive behavior of AD-model mice. Further studies on the structural optimization of this series of derivatives are currently underway in our laboratory.

Elemental-Sulfur-Enabled Divergent Synthesis of Disulfides, Diselenides, and Polythiophenes from ß-CF3 -1,3-Enynes.

Divergent synthesis for precise constructions of cyclic unsymmetrical diaryl disulfides or diselenides and polythiophenes from CF3 -containing 1,3-enynes and S8 was developed when the ortho group is F, Cl, Br, and NO2 on aromatic rings. Meanwhile, disulfides (diselenides) were also quickly constructed when the ortho group is H. These transformations undergo cascade thiophene construction/selective C3-position thiolation process, featuring simple operations, divergent synthesis, broad substrate scope, readily available starting materials, and valuable products. A novel plausible radical annulation process was proposed and validated by DFT calculations for the first time. A series of derivatizations about the thiophene (TBT) and disulfides were also well-represented.

Five-year study on the effects of warming and plant litter quality on litter decomposition rate in a Tibetan alpine grassland.

The decomposition of plant litter is a key link in global C budgets and provides strong feedback to changes in climate and biogeochemical cycles. However, the combined effects of global warming and plant litter quality on the rate of plant litter decomposition and nutrient dynamics in alpine ecosystems are still poorly understood. We conducted a warming experiment to investigate the effects of litter quality and temperature on decomposition rates and variations in nutrients of four common herbaceous plants (low-quality litter species Stipa purpurea and Carex moorcroftii and high-quality litter species Astragalus confertus and Leontopodium nanum) during 2011-2016. During the initial stages of decomposition, warming had no significant effect on the mass loss of plant litter for low-quality litter species, but in the later stages of decomposition, it had a negative effect on the mass loss across all species (P < 0.05). Litter quality was the best predictor of N and P release/immobilisation during the decomposition of aboveground plant litter. Low-quality litter had the highest immobilisation of N at about 80% of the initial remaining mass; nutrients were then released in the following stages of decomposition. However, the fraction of initial P decreased with the mass remaining during the initial and later phases of decomposition, but a short period of P immobilisation occurred in the middle phase of decomposition. For high-quality litter, the fraction of initial N and P decreased with the mass remaining during the whole decomposition process. Warming had a marginal influence on the N and P dynamics throughout the decomposition process. Our study showed that the decay of plant litter was strongly suppressed by warming climate and that the N and P dynamics on the investigated Tibetan grassland were mainly regulated by litter quality, providing valuable insights into the biogeochemical cycles of nutrients in alpine ecosystems.