Amide-Directed, Rhodium-Catalyzed Regio- and Enantioselective Hydroacylation of Internal Alkenes with Unfunctionalized Aldehydes.

Despite the current progress achieved in asymmetric hydroacylations, highly enantioselective catalytic addition of unfunctionalized aldehydes to internal alkenes remains an unsolved challenge. Here, using a coordination-assisted strategy, we developed a rhodium-catalyzed regio- and enantioselective addition of unfunctionalized aldehydes to internal alkenes such as enamides and ß,γ-unsaturated amides. Valuable α-amino ketones and 1,4-dicarbonyl compounds were directly obtained with high enantioselectivity from readily available materials.

Rhodium-Catalyzed Highly Enantioselective Hydroboration of Acyclic Tetrasubstituted Alkenes Directed by an Amide.

Although progress has been made in enantioselective hydroboration of di- and trisubstituted alkenes over the past decades, enantioselective hydroboration of tetrasubstituted alkenes with high diastereo- and enantioselectivities continues as an unmet challenge since the 1950s due to its extremely low reactivity and the difficulties to simultaneously control the regio- and stereoselectivity of a tetrasubstituted alkene. Here, we report highly regio-, diastereo-, and enantioselective catalytic hydroboration of diverse acyclic tetrasubstituted alkenes. The delicate interplay of an electron-rich rhodium complex and coordination-assistance forms a highly adaptive catalyst that effectively overcomes the low reactivity and controls the stereoselectivity. The generality of the catalyst system is exemplified by its efficacy across various tetrasubstituted alkenes with diverse steric and electronic properties.

One-Step Electrochemical Ethylene-to-Ethylene Glycol Conversion over a Multitasking Molecular Catalyst.

Ethylene glycol is an essential commodity chemical with high demand, which is conventionally produced via thermocatalytic oxidation of ethylene with huge fossil fuel consumption and CO2 emission. The one-step electrochemical approach offers a sustainable route but suffers from reliance on noble metal catalysts, low activity, and mediocre selectivity. Herein, we report a one-step electrochemical oxidation of ethylene to ethylene glycol over an earth-abundant metal-based molecular catalyst, a cobalt phthalocyanine supported on a carbon nanotube (CoPc/CNT). The catalyst delivers ethylene glycol with 100% selectivity and 1.78 min-1 turnover frequency at room temperature and ambient pressure, more competitive than those obtained over palladium catalysts. Experimental data demonstrate that the catalyst orchestrates multiple tasks in sequence, involving electrochemical water activation to generate high-valence Co-oxo species, ethylene epoxidation to afford an ethylene oxide intermediate via oxygen transfer, and eventually ring-opening of ethylene oxide to ethylene glycol facilitated by in situ formed Lewis acid site. This work offers a great opportunity for commodity chemicals synthesis based on a one-step, earth-abundant metal-catalyzed, and renewable electricity-driven route.

Coordination Assistance: A Powerful Strategy for Metal-Catalyzed Regio- and Enantioselective Hydroalkynylation of Internal Alkenes.

ConspectusAlkenes are versatile compounds that are readily available on a large scale from industry or through organic synthesis. The widespread occurrence of alkenes provides the continuous impetus for the development of catalytic asymmetric alkene hydrofunctionalizations, which enables expeditious construction of complex chiral molecules from readily available starting materials. Catalytic asymmetric hydrofunctionalization of internal alkenes presents a notable challenge, due to their low reactivity, many potential side reactions, and the simultaneous control of the regio-, diastereo-, and enantioselectivities.Dehydroamino acids and enamides are among the first substrates that provide notable enantioselectivities in catalytic asymmetric hydrogenation. The crucial importance of an amide coordinating group is established by a series of classical mechanistic studies. This initial success greatly stimulated further development for catalytic hydrogenation and hydrofunctionalization. Building on these pioneering works in asymmetric hydrogenation as well as related hydrofunctionalizations, we have adopted coordination assistance as a powerful tool to address the challenges associated with the asymmetric hydrofunctionalization of internal alkenes. Using a functional group on the alkene substrate as a native coordinating group, a two-point binding mode of the substrate to the metal center effectively enhances the reactivity and facilitates the control of regio-, diastereo- and enantioselectivities. Through this strategy, we have developed a number of alkene hydrofunctionalization methods with excellent regio-, diastereo-, and enantiocontrols.In this Account, we summarize the recent advance in our lab using coordination assistance as a key element to achieve regio- and enantioselective hydroalkynylation of internal alkenes. First, we describe our early work aimed at controlling the regio- and enantioselectivity of hydroalkynylation using disubstituted enamide as the substrate. Both α- and ß-alkynylation were achieved by channeling the reaction pathway into a Chalk-Harrod or modified Chalk-Harrod mechanism. Next, we discuss the further development of catalysts to achieve regiodivergent and enantioselective hydroalkynylation of trisubstituted enamide to access vicinal stereocenters and quaternary carbon stereocenters. We also discuss the hydroalkynylation of α,ß-unsaturated amides to achieve unconventional site-selectivity through a combination of alkene isomerization and regioselective hydroalkynylation. This provides the basis for the construction of a remote quaternary carbon stereocenter through catalytic hydroalkynylation of trisubstituted ß,γ-unsaturated amides. We further show that this controlling principle is applicable to terminal alkene with a coordinating group as well. A ligand-controlled mechanism shift is discussed for the enantioselective alkynylation at the terminal and internal position of 1,1,-disubstituted alkenes. Finally, we briefly mention the application of coordination assistance to other hydrofunctionalizations such as hydroboration and hydrosilylation, where previously inaccessible reactivity and selectivity were achieved. Collectively, these catalytic methods demonstrate the power of coordination assistance for enantioselective hydrofunctionalizations. We anticipate that this strategy will create a platform to enable diverse enantioselective alkene transformations.

Directing Group Repositioning Strategy Enabled Site- and Enantioselective Addition of Heteroaromatic C-H Bonds to Acyclic Internal Alkenes.

Despite the notable advances achieved in the Murai-type hydroarylations, highly enantioselective catalytic addition of native (hetero)arenes to internal alkenes remains a prominent challenge. Herein, we report a directing group repositioning strategy, which enables the iridium-catalyzed enantioselective addition of heteroarenes including furan, benzofuran, and thiophene to internal enamides. The C-H bond at the C2 position of the heteroarene is site-selectively cleaved and added regioselectively to the ß-position of an enamide, affording a valuable ß-heteroaryl amide with high enantioselectivity. Mechanistic studies indicate that the rate and the enantioselectivity are determined by separate elementary steps.

Value of biplane transrectal ultrasonography plus micro-flow imaging in preoperative T staging and rectal cancer diagnosis in combination with CEA/CA199 and MRI.

BACKGROUND: Rectal cancer is one of the most common malignant tumors and has a high incidence rate and fatality rate. Accurate preoperative T staging of rectal cancer is critical for the selection of appropriate rectal cancer treatment. Various pre-operative imaging methods are available, and the identification of the most accurate method for clinical use is essential for patient care. We investigated the value of biplane transrectal ultrasonography (TRUS) combined with MFI in preoperative staging of rectal cancer and explored the value of combining TRUS plus MFI with CEA/CA199 and MRI. METHODS: A total of 87 patients from Daping Hospital with rectal cancer who underwent TRUS examination plus MFI were included. Grades of MFI were determined by Alder classification. Among the total patients, 64 underwent MRI and serum CEA/CA199 tests additionally within one week of TRUS. Pathological results were used as the gold standard for cancer staging. Concordance rates between TRUS, MRI, and CEA/CA199 for tumors at different stages were compared. RESULTS: There were no significant differences between the Alder classification and pathological T staging. The concordance rate of TRUS and MFI for rectal cancer T staging was 72.4% (K = 0.615, p < 0.001). Serum CEA and CA199 levels were significantly different in tumors at different stages and increased progressively by pathological stage (p < 0.001); the accuracy rate was 71.88% (K = 0.599, p < 0.001), while that of MRI was 51.56% (K = 0.303, p < 0.001), indicating that TRUS had higher consistency in the preoperative T staging of rectal cancer. The combination of TRUS, MRI, and CEA/CA199 yielded an accuracy rate of 90.6%, which was higher than that of any method alone. CONCLUSIONS: Preoperative T staging of rectal cancer from biplane TRUS plus MFI was highly consistent with postoperative pathological T staging. TRUS combined with MRI and serum CEA/CA199 had a greater value in the diagnosis of rectal cancer and a higher diagnostic rate than any examination alone.

The component of the Chamaecyparis obtusa essential oil and insecticidal activity against Tribolium castaneum (Herbst).

Tribolium castaneum (Herbst) is a worldwide grain storage pest controlled by chemical control methods of phosphine fumigation, which results in many hazards, damages human health, makes pests resistant to pesticides, and pollutes the environment. In recent years, the popularity of botanical insecticides has continued to rise, and plant essential oils (EO) are considered potential alternatives for developing insecticides. In the current study, we selected the Chamaecyparis obtusa EO to determine its insecticidal effects and component analysis on T. castaneum. Through gas chromatography-ion mobility spectrometry (GC-IMS) technology, cedrol was the most obvious compound in the signal peak of the volatile components detected in the C. obtusa EO. The results of the bioassay showed that the C. obtusa EO had certain contact activity against T. castaneum, and the LD50 was 52.54 µg/adult. At three concentrations (0.41,1.62, 2.83 uL/cm2), the repellent rates of C. obtusa EO against T. castaneum were all above 80% at 15, 30, 60, and 120 min, respectively, indicating that the repellent effect was strong. Meanwhile, the C. obtusa EO exhibited fumigant toxicity against T. castaneum with LC50 values of 7.09 µg/L air. In addition, C. obtusa EO significantly increased the activity of AChE, CarE, POD, CAT, T-SOD, and chitinase in T. castaneum. Finally, the mechanism of C. obtusa EO on T. castaneum adults was explored based on transcriptome sequencing. We found that the DEGs focused on the chitin metabolic process and some aging genes in T. castaneum. Therefore, C. obtusa EO could be used as potential eco-friendly candidates for stored grain pest management.

Enantioselective Hydrosilylation of ß,ß-Disubstituted Enamides to Construct α-Aminosilanes with Vicinal Stereocenters.

Despite the advances in the area of catalytic alkene hydrosilylation, the enantioselective hydrosilylation of alkenes bearing a heteroatom substituent is scarce. Here we report a rhodium-catalyzed hydrosilylation of ß,ß-disubstituted enamides to directly afford valuable α-aminosilanes in a highly regio-, diastereo-, and enantioselective manner. Stereodivergent synthesis could be achieved by regulating substrate geometry and ligand configuration to generate all the possible stereoisomers in high enantio-purity.

Iridium-Catalyzed Branch-Selective and Enantioselective Hydroalkenylation of α-Olefins through C-H Cleavage of Enamides.

Catalytic branch-selective hydrofunctionalization of feedstock α-olefins to form enantioenriched chiral compounds is a particularly attractive yet challenging transformation in asymmetric catalysis. Herein we report an iridium-catalyzed asymmetric hydroalkenylation of α-olefins through directed C-H cleavage of enamides. This atom-economical addition process is highly branch-selective and enantioselective, delivering trisubstituted alkenes with an allylic stereocenter. DFT calculations reveal the origin of regio- and enantioselectivity.

Remote Stereocenter through Amide-Directed, Rhodium-Catalyzed Enantioselective Hydroboration of Unactivated Internal Alkenes.

Despite the frequent occurrence of γ-branched amines in bioactive molecules, the direct catalytic asymmetric synthesis of this structural motif containing a remote stereocenter remains an important synthetic challenge. Here, we report an amide-directed, rhodium-catalyzed highly diastereo- and enantioselective hydroboration of unactivated internal alkenes. This method provided facile access to enantioenriched amines containing ß,γ-vicinal stereocenters. The application of this strategy to the synthesis of bioactive molecules was demonstrated. Computational studies indicated that migratory insertion of the alkene into rhodium hydride controls the enantioselectivity.

Isotherm, Thermodynamics, and Kinetics of Methyl Orange Adsorption onto Magnetic Resin of Chitosan Microspheres.

Severe environmental pollution problems arising from toxic dyestuffs (e.g., methyl orange) are receiving increasing attention. Therefore, dyes' safe removal has become a research hotspot. Among the many physical-chemical removal techniques, adsorption using renewable biological resources has proved to be more advantageous over others due to its effectiveness and economy. Chitosan is a natural, renewable biopolymer obtained by deactivated chitin. Thus, the magnetic resin of chitosan microspheres (MRCM), prepared by reversed-phase suspension cross-linking polymerization, was used to remove methyl orange from a solution in a batch adsorption system. The main results are as follows: (1) The results of physical and swelling properties of MRCM indicated that MRCM was a type of black spherical, porous, water-absorbing, and weak alkali exchange resin, and it had the ability to adsorb methyl orange when it was applied in solutions above pH 2.0. (2) In batch adsorption studies, the maximum adsorption capacity was obtained at pH 5; the adsorption equilibrium time was 140 min; and the maximum adsorption was reached at 450 mg/L initial concentration. (3) Among the three isotherm adsorption models, Langmuir achieved the best fit for the adsorption of methyl orange onto MRCM. (4) The adsorption thermodynamics indicated that the adsorption was spontaneous, with increasing enthalpy, and was driven by the entropy. (5) The pseudo-second-order kinetics equation was most suitable to describe the adsorption kinetics, and the adsorption kinetics was also controlled by the liquid-film diffusion dynamics. Consequently, MRCM with relatively higher methyl orange adsorption exhibited the great efficiency for methyl orange removal as an environment-friendly sorbent. Thus, the findings are useful for methyl orange pollution control in real-life wastewater treatment applications.

Dextran Fluorescent Probes Containing Sulfadiazine and Rhodamine B Groups.

Fluorescent imaging has been expanded, as a non-invasive diagnostic modality for cancers, in recent years. Fluorescent probes in the near-infrared window can provide high sensitivity, resolution, and signal-to-noise ratio, without the use of ionizing radiation. Some fluorescent compounds with low molecular weight, such as rhodamine B (RhB) and indocyanine green (ICG), have been used in fluorescent imaging to improve imaging contrast and sensitivity; however, since these probes are excreted from the body quickly, they possess significant restrictions for imaging. To find a potential solution to this, this work investigated the synthesis and properties of novel macromolecular fluorescent compounds. Herein, water-soluble dextran fluorescent compounds (SD-Dextran-RhB) were prepared by the attachment of RhB and sulfadiazine (SD) derivatives to dextran carrier. These fluorescent compounds were then characterized through IR, 1H NMR, 13C NMR, UV, GPC, and other methods. Assays of their cellular uptake and cell cytotoxicity and fluorescent imaging were also performed. Through this study, it was found that SD-Dextran-RhB is sensitive to acidic conditions and possesses low cell cytotoxicities compared to normal 293 cells and HepG2 and HeLa tumor cells. Moreover, SD-Dextran-RhB demonstrated good fluorescent imaging in HepG2 and HeLa cells. Therefore, SD-Dextran-RhB is suitable to be potentially applied as a probe in the fluorescent imaging of tumors.

Iridium-Catalyzed Regiodivergent and Enantioselective Hydroalkynylation of Unactivated 1,1-Disubstituted Alkenes.

Catalytic enantioselective functionalization of unactivated 1,1-disubstituted alkenes is challenging due to the difficulty to discriminate the enantiotopic faces. Enantioselective hydrofunctionalization of unactivated 1,1-disubstituted alkenes with tunable Markovnikov and anti-Markovnikov selectivity remains elusive. We report here an amide-directed, regiodivergent and enantioselective hydroalkynylation of unactivated alkenes. The regioselectivity can be readily tuned by the choice of a proper ligand. Catalytic alkynylations occurred with tunable Markovnikov and anti-Markovnikov selectivity to afford products containing acyclic tertiary or quaternary stereocenters ß to an amide. Combining a sequence of alkene isomerization and regioselective hydroalkynylation, we further realized an iridium-catalyzed formal asymmetric conjugated alkynylation of ß,ß-disubstituted α,ß-unsaturated amides. Computational studies suggest that the regioselectivity is dictated by the ligand structures.

Stereodefined Skipped Dienes through Iridium-Catalyzed Formal Addition of Tertiary Allylic C-H Bonds to Alkynes.

Preparation of skipped dienes with a quaternary carbon center at the C-3 position remains a synthetic challenge. We report here an iridium-catalyzed formal addition of tertiary sp3 C-H bond to alkyne for the facile preparation of skipped dienes. The tertiary allylic C-H bond is cleaved regioselectively, at the site of which a new C-C bond is formed. Enantioselective construction of acyclic quaternary carbon stereocenters is also demonstrated.

Ir-Catalyzed Regio- and Enantioselective Hydroalkynylation of Trisubstituted Alkene to Access All-Carbon Quaternary Stereocenters.

The stereoselective construction of all-carbon quaternary stereocenters, especially acyclic ones, represents an important challenge in organic synthesis. In particular, homopropargyl amides with a quaternary stereocenter ß to a nitrogen atom are valuable synthetic intermediates, which could be transformed to diverse chiral structures through alkyne transformations. However, highly enantioselective synthetic methods for homopropargyl amides with a ß quaternary stereocenter are extremely rare. We report here unprecedented substrate-directed, iridium-catalyzed enantioselective hydroalkynylations of trisubstituted alkenes to form an acyclic all-carbon quaternary stereocenter ß to a nitrogen atom. The hydroalkynylation of enamide occurred with unconventional selectivity, favoring the more hindered reaction site. Homopropargyl amides with ß-stereocenters were prepared in high regio- and enantioselectivities. Combined experimental and computational studies revealed the origin of the regio- and enantioselectivities.

Pseudomonas laoshanensis sp. nov., isolated from peanut field soil.

A novel Gram-stain-negative, aerobic strain, designated Y22T, was isolated from peanut field soil in Laoshan Mountain in China. Cells of strain Y22T were rod-shaped and motile by a single flagellum. The strain was found to be oxidase- and catalase-positive. 16S rRNA gene sequence based on phylogenetic analysis indicated that strain Y22T belonged to the genus Pseudomonas, and showed the highest 16S rRNA gene sequence similarity of 99.0% to Pseudomonas pelagia JCM 15562T, followed by Pseudomonas salina JCM 19469T (98.4%), Pseudomonas sabulinigri JCM 14963T (97.9%), Pseudomonas bauzanensis CGMCC 1.9095T (97.6%) and Pseudomonas litoralis KCTC23093T (97.5%). The phylogenetic analysis based on multilocus sequence analyses with concatenated 16S rRNA, gyrB, rpoD and rpoB genes indicated that strain Y22T belonged to Pseudomonas pertucinogena lineage. The average nucleotide identity scores between strain Y22T and closely related species were 74.6-82.8%, and the Genome-to-Genome Distance Calculator scores were 16.4-44.9%. The predominant cellular fatty acids of strain Y22T were C18:1ω7c (29.6%), C17:0 cyclo (17.5%) and summed feature 3 (C16:1ω7c and/or C16:1ω6c) (17.4%). The genomic DNA G+C content was 57.9 mol%. On the basis of phenotypic characteristics, phylogenetic analyses and in silico DNA-DNA relatedness, a novel species, Pseudomonas laoshanensis sp. nov. is proposed. The type strain is Y22T (= JCM 32580T = KCTC 62385T = CGMCC 1.16552T).

[Effects of Acrolein on the Proliferation of and Per1 Gene Expression in Pulmonary Epithelial Cells].

OBJECTIVE: To investigate the effect of acrolein on the proliferation of pulmonary epithelial cells and its possible mechanism. METHODS: Two strains of pulmonary epithelial cells, A549 cells and MLE15 cells, were used as in vitro models of pulmonary epithelial cell, and were treated with 80 µmol/L acrolein or phosphate buffer saline (PBS) as the control. The proliferation of pulmonary epithelial cells were determined with CCK-8 kit after cell culturing resumed for 12 h, 24 h, 36 h and 48 h post acrolein treatment, and the expression of period circadian regulator gene 1 ( Per1) was examined using Western blot test 24 h after acrolein treatment. In addition, after acrolein treatment, the cells were restored with transforming growth factor-ß (TGF-ß) added in the medium, and the cell proliferation and the expression of Per1 protein were also examined. RESULTS: The proliferation of A549 cells and MLE15 cells decreased significantly after being treated with 80 µmol/L acrolein for 30 min, and the expression of Per1 protein was also downregulated significantly ( P<0.05). The addition of TGF-ß after acrolein treatment did not significantly change the reduction in cell proliferation caused by acrolein, but the expression of Per1 protein in pulmonary epithelial cells was significantly higher than that in cells restored without TGF-ß ( P<0.05). CONCLUSION: Acrolein treatment resulted in the decreased proliferation of pulmonary epithelial cells and the Per1 expression in pulmonary epithelial cells. Although TGF-ß addition did not reverse the reduction of cell proliferation after acrolein treatment, the Per1 expression levels were recovered to a certain extent compared to that in cells restored in medium without TGF-ß after acrolein treatment.

Searching new structures of beryllium-doped in small-sized magnesium clusters: Be2 Mgn Q (Q = 0, -1; n = 1-11) clusters DFT study.

Using CALYPSO method to search new structures of neutral and anionic beryllium-doped magnesium clusters followed by density functional theory (DFT) calculations, an extensive study of the structures, electronic and spectral properties of Be2 Mgn Q (Q = 0, -1; n = 2-11) clusters is performed. Based on the structural optimization, it is found that the Be2 Mgn Q (Q = 0, -1) clusters are shown by tetrahedral-based geometries at n = 2-6 and tower-like-based geometries at n = 7-11. The calculations of stability indicate that Be2 Mg5 Q=0 , Be2 Mg5 Q=-1 , and Be2 Mg8 Q=-1 clusters are "magic" clusters with high stability. The NCP shows that the charges are transferred from Mg atoms to Be atoms. The s- and p-orbitals interactions of Mg and Be atoms are main responsible for their NEC. In particular, chemical bond analysis including molecular orbitals (MOs) and chemical bonding composition for magic clusters to further study their stability. The results confirmed that the high stability of these clusters is due to the interactions between the Be atom and the Mg5 or Mg8 host. Finally, theoretical calculations of infrared and Raman spectra of the ground state of Be2 Mgn Q (Q = 0, -1; n = 1-11) clusters were performed, which will be absolutely useful for future experiments to identify these clusters.

A quasi-plane IrB18- cluster with high stability.

The structural evolution of neutral and anionic iridium-doped boron (B) clusters, IrBn0/- with n = 10-20, has been studied by the Crystal structure AnaLYsis by Particle Swarm Optimization (CALYPSO) method and density functional theory (DFT) calculations. The IrB18- cluster with a quasi-plane structure and high stability is uncovered. Molecular orbital (MO) and adaptive natural density partitioning (AdNDP) analyses indicate that the high stability of the IrB18- cluster is attributed to the strong covalent interactions between the 5d orbitals of the Ir atom and the 2p orbitals of the surrounding B atoms. The present results offer new insights and considerably extend our understanding of the structural evolution and electronic properties of other metal-doped B clusters.

Highly Enantioselective Synthesis of Propargyl Amide with Vicinal Stereocenters through Ir-Catalyzed Hydroalkynylation.

Chiral propargyl amines are valuable synthetic intermediates for the preparation of biologically active compounds and functionalized amines. Catalytic methods to access propargyl amines containing vicinal stereocenters with high diastereoselectivity are particularly rare. We report an unprecedented strategy for the synthesis of enantioenriched propargyl amines with two stereogenic centres. An iridium complex, ligated by a phosphoramidite ligand, catalyzes the hydroalkynylation of ß,ß-disubstituted enamides to afford propargyl amides in a highly regio-, diastereo-, and enantioselective fashion. Stereodivergent synthesis of all four possible stereoisomers was achieved using this strategy.