Aryl-to-Vinyl 1,4-Nickel Migration/Reductive Cross-Coupling Reaction for the Stereoselective Synthesis of Multisubstituted Olefins.

The aryl-to-vinyl nickel 1,4-migration (1,4-Ni migration) reaction has been reported for the first time. The generated alkenyl Ni species undergo a reductive coupling reaction with unactivated brominated alkanes affording a series of trisubstituted olefins. This tandem reaction exhibits mild conditions, a broad substrate scope, high regioselectivity, and excellent Z/E stereoselectivity. A series of controlled experiments have shown that the critical 1,4-Ni migration process is reversible. In addition, the alkenyl nickel intermediates obtained after migration are highly Z/E stereoselective and do not undergo Z/E isomerization. The obtained trace isomerization products are caused by the instability of the product.

Ruthenium-Catalyzed Stereo- and Site-Selective ortho- and meta-C-H Glycosylation and Mechanistic Studies.

C-aryl glycosides are popular basic skeletons in biochemistry and pharmaceutical chemistry. Herein, ruthenium-catalyzed highly stereo- and site-selective ortho- and meta-CAr -H glycosylation is described. A series of C-aryl pyranosides and furanosides were synthesized by this method. The strategy showed good substrate scope, and various N-heterocyclic directing groups were compatible with the reaction system. A mechanistic study suggested that the key pathway of ortho-CAr -H glycosylation might involve oxidative addition/reduction elimination, whereas aryl meta-C-H glycosylation was mediated by σ-activation. Density functional theory calculations also showed that the high stereoselectivity of meta-CAr -H glycosylation was due to steric hindrance.

[Allergen Analysis of 4622 Children with Allergic Diseases in Shaanxi Province].

OBJECTIVE: To study the distributional characteristics of allergens in children with allergic diseases in Shaanxi province. METHODS: A total of 4 622 children diagnosed with allergic diseases in the Asthma Center, Department of Pediatrics, Xijing Hospital from March 2015 to February 2019 were selected. Serum allergen-specific immunoglobulin E (sIgE) of 19 common kinds of allergens were examined with enzyme-linked immunosorbent assay (ELISA). The children were divided into different groups according to sex, age and geographical regions, and the distributional characteristics of allergens of the different groups were compared. RESULTS: The overall positive rate for the 19 allergens of the 4 622 children was 62.8%. The ranking of the positive rates for individual allergens from high to low were as follows: 24.2% for milk, 18.0% for mold mix, 16.7% for dog dander, 16.4% for house dust mite, 11.7% for cat dander, 10.7% for cashew, 10.6% for weed pollen, 8.8% for egg white, 7.8% for house dust, 7.7% for tree pollen, 5.6% for amaranth, 4.9% for mulberry tree, 3.6% for mango, 3.2% for beef, 2.8% for cockroach, 2.1% for crab, 1.5% for shrimp, 0.8% for pineapple, and 0.3% for shellfish. Analysis based on sex showed that the allergen positive rates in boys were higher than those in girls. Analysis by age difference showed that generally the positive rates for inhaled allergens increased along with the increase in patient age, while the positive rates for ingested allergens decreased along with the increase in patient age. Analysis by geographical regions showed that the positive rate of house dust mite in the patients from the southern part of Shaanxi, the positive rate of weed pollen in the patients from the northern part of Shaanxi and the positive rates of milk and egg white in the patients from the central part of Shaanxi were higher than those in other areas. The cluster analysis and correlation analysis showed that the 19 allergens could be roughly divided into 4 categories. There were moderate correlations among tree pollen, mulberry tree and amaranth. There were moderate correlations among mulberry tree, mango and amaranth. There was moderate correlation between shrimp and crab, and there were mild or weak correlations among most of the other allergens. CONCLUSION: Among the 4 622 children with allergic diseases in Shaanxi Province who were treated in the Asthma Center, Department of Pediatrics, Xijing Hospital, male patients showed higher sensitivity to allergens. The positive rates of inhaled allergens increased, while the positive rates of ingested allergens decreased with increase in patient age. There were regional differences in the distribution of allergens. Some allergens were correlated with each other, which may be related to cross-reaction.

Copper-Catalyzed Three-Component Redox-Neutral Ring Opening of Benzothiazoles to 1-Amino-N-(2-(phenylthio)phenyl)methanimine.

Copper-catalyzed three-component redox-neutral ring opening of benzothiazoles with aryl iodides and O-benzoyl hydroxylamines for the synthesis of 1-amino-N-(2-(phenylthio)phenyl)methanimine has been developed. This one-pot reaction undergoes C-S and N-O bond cleavage and new C-S and C-N bond construction. Several control experiments excluded a free radical procedure and also demonstrated the secondary amine as a possible intermediate, which was vital to the catalytic reaction. Meanwhile, the deuteration experiment got rid of the C-H activation dehydroisomerization of the benzothiazole mechanism.

Palladium-Catalyzed ortho-C-H Glycosylation/ipso-Alkenylation of Aryl Iodides.

This report describes the first example of palladium-catalyzed ortho-C-H glycosylation/ipso-alkenylation of aryl iodides, and the easily accessible glycosyl chlorides are used as a glycosylation reagent. The reaction is compatible with the functional groups of the substrates, and a series of C-aryl glycosides have been synthesized in good to excellent yield and with excellent diastereoselectivity. It is found that a cheap 5-norbornene-2-carbonitrile as a transient mediator can effectively promote this reaction. In addition, ipso-arylation and cyanation were also realized by the strategy.

Rapid colorimetric determination of dopamine based on the inhibition of the peroxidase mimicking activity of platinum loaded CoSn(OH)6 nanocubes.

Platinum nanoparticles were loaded on CoSn(OH)6 nanocubes via a co-precipitation method. The material (NCs) is shown to be a viable peroxidase mimic that catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by hydrogen peroxide (H2O2) to generate oxidized TMB (oxTMB) with absorption at 652 nm. The formation of the blue color can be observed in <30 s. Thus, a visual and colorimetric assay was worked out for H2O2. It has a detection limit as low as 4.4 µM and works in the 5 to 200 µM concentration range. The method was also used to detect dopamine (DA) which is found to inhibit the enzyme mimicking activity of the NCs. Hence, less blue color is formed in its presence. The respective DA assay has a linear response in the 5.0 to 60 µM concentration range and a 0.76 µM detection limit. Graphical abstractSchematic diagram of a visual colorimetric method for determination of H2O2 and dopamine (DA) with the aid of color change of 3,3',5,5'-tetramethylbenzidine (oxTMB), based on the peroxidase-like activity of Pt/CoSn(OH)6 nanocubes.

Stereoselective assembly of C-oligosaccharides via modular difunctionalization of glycals.

C-oligosaccharides are found in natural products and drug molecules. Despite the considerable progress made during the last decades, modular and stereoselective synthesis of C-oligosaccharides continues to be challenging and underdeveloped compared to the synthesis technology of O-oligosaccharides. Herein, we design a distinct strategy for the stereoselective and efficient synthesis of C-oligosaccharides via palladium-catalyzed nondirected C1-H glycosylation/C2-alkenylation, cyanation, and alkynylation of 2-iodoglycals with glycosyl chloride donors while realizing the difunctionalization of 2-iodoglycals. The catalysis approach tolerates various functional groups, including derivatives of marketed drugs and natural products. Notably, the obtained C-oligosaccharides can be further transformed into various C-glycosides while fully conserving the stereochemistry. The results of density functional theory (DFT) calculations support oxidative addition mechanism of alkenyl-norbornyl-palladacycle (ANP) intermediate with α-mannofuranose chloride and the high stereoselectivity of glycosylation is due to steric hindrance.

Photoredox-Catalyzed N-Directed Regioselective Difluoroalkylation of Unactivated C(sp3)-H Bonds.

We report a redox-neutral, visible-light-mediated difluoroalkylation of unactivated C(sp3)-H bonds in amides via nitrogen-centered radicals triggered intramolecular hydrogen atom transfer. Notably, all types (tertiary, secondary, and primary) of γ-C(sp3)-H bonds displayed excellent reactivity. This methodology presents a facile route for the regioselective introduction of α,α-difluoroketone fragments into organic molecules. Moreover, the resulting gem-difluoroketones can be readily converted to structurally diverse difluoro-containing molecules, offering broad potential applications in medicinal chemistry and chemical biology.

Visible-Light-Mediated Synthesis of C-Alkyl Glycosides via Glycosyl Radical Addition and Aryl Migration.

A visible-light-induced glycoarylation of activated olefins has been accomplished. Glycosyl radicals are generated via radical transfer strategies between (TMS)3SiOH and glycosyl bromides. Subsequent radical translocation and rapid 1,4-aryl migration form ß-sugar amide derivatives, and eight types of sugars are compatible with this reaction. Further, the cascade reaction produced a quaternary carbon center with good functional group adaptability and high regioselectivity in mild conditions.

[Clinical significance of skin prick test for inhalant allergens in 3085 children with allergic diseases].

OBJECTIVE: To investigate the main inhalant allergens and their distribution patterns in children with allergic diseases from Xi'an and the surrounding area and to provide evidence for the prevention and treatment of allergic diseases in children. METHODS: Skin prick test was performed using liquid with 13 standardized allergens (ALK-ABELL, Denmark) on 3085 children from Xi'an and the surrounding area who were treated for allergic diseases between July 2006 and July 2011, to detect inhalant allergens. RESULTS: Of the 3085 patients, 1368 (44.34%) had positive SPT results, with the most prevalent inhalant allergen being Dermatophagoides pteronyssinus (804 cases, 26.06%), followed by Dermatophagoides farinae (793 cases, 25.71%), Blomia tropicalis (440 cases, 14.26%), mugwort (282 cases, 9.14%), and cat hair (204 cases, 6.61%). The positive rates were 28.66% in the <4 years group, 41.85% in the 4-6 years group, and 58.61% in the 7-15 years group (P<0.01). Males had a significantly higher SPT positive rate than females (47.78% vs 38.50%；P<0.05). The SPT positive rate was highest in children with allergic rhinitis (72.41%), followed by bronchial asthma (62-25%), allergic dermatosis (45.83%), and allergic purpura (36.28%). CONCLUSIONS: In children from Xi'an and the surrounding area, the main inhalant allergens for allergic diseases include Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicalis, mugwort and cat hair. The SPT positive rate increases with age. Male children have a higher SPT positive rate than female children. The SPT positive rate is highest in children with allergic rhinitis.

Visible-Light-Induced Copper-Catalyzed Asymmetric C(sp3)-C(sp3)-H Glycosylation: Access to C-Glycopeptides.

Herein, a practical and highly efficient method for visible-light-induced copper-catalyzed N-aminoquinoline-directed asymmetric C(sp3)-C(sp3)-H glycosylation was reported. At the same time, C(sp3)-C(sp3)-H glycosylation of nondeoxysugars with amino acids to construct C-glycopeptides was achieved. This approach promoted the synthesis of various C-glycopeptides and provided a new model for the synthesis of C-glycoamino acids.

Palladium-catalyzed rearrangement reaction to access 1-phenanthrol derivatives.

This manuscript describes an unusual Pd-catalyzed rearrangement reaction. It provides efficient access to 1-phenanthrol derivatives using allyloxy-tethered aryl iodides. This rearrangement process involves the cleavage of a C-I bond, a C-O bond and C-H bonds, and the formation of two C-C bonds in one-pot. It is likely that the key to the success of this rearrangement is via ß-carbon elimination from a strained palladacycle.

Enantioselective Synthesis of Both Axially and Planar Chiral Ferrocenes via Axial-to-Planar Diastereoinduction.

Ferrocenes with planar chirality have emerged as an important class of scaffolds for ligands in asymmetric catalysis; however, ferrocene molecules with polychiral structures have not been well explored. Herein, both axially and planar chiral ferrocenes were synthesized via palladium/chiral norbornene cooperative catalysis and axial-to-planar diastereoinduction. In this work, chiral norbornene was used to stereoselectively control the aromatic axial chirality, and further selectivity induced C(sp2)-H activation for ferrocene planar chirality. Based on density functional theory calculations, the catalytic model of chiral norbornene with the substrate and the axial-to-planar diastereoinduction process were confirmed.

One-Pot Stereoselective Synthesis of 2,3-Diglycosylindoles and Tryptophan-C-glycosides via Palladium-Catalyzed C-H Glycosylation of Indole and Tryptophan.

We described a novel palladium-catalyzed C-H glycosylation of indole or tryptophan for a one-pot stereoselective synthesis of 2,3-diglycosylindoles and tryptophan-C-glycosides. In this strategy, the use of air and base-free and ligand-free conditions provided a highly efficient route to construct C-glycosides. The method can be applied to a wide range of cost-effective and convenient glycosyl chloride donors. Mechanistic studies indicated that the indole 2,3-diglycosylation sequence was C3 and then C2.

Palladium-Catalyzed C-H Amination/[2 + 3] or [2 + 4] Cyclization via C(sp3 or sp2)-H Activation.

This report describes a palladium-catalyzed Catellani reaction consisting of amination/[2 + 3] or [2 + 4] cyclization via a carboxylate ligand-exchange strategy. This method effectively activates ortho-substituents that avoid a second C-H palladation. The scope of substrates was broad, o-methyl-substituted iodoarenes were applied to the reaction smoothly, and o-phenyl-substituted iodoarenes can also be obtained by this method. In terms of mechanism, density functional theory calculations proved the sequence of the key five-membered aryl-norbornene-palladacycle intermediate formation and C(sp3 or sp2)-H activation.

Palladium-Catalyzed Chemoselective Oxidative Addition of Allyloxy-Tethered Aryl Iodides: Synthesis of Medium-Sized Rings and Mechanistic Studies.

This Letter describes a Pd-catalyzed Tsuji-Trost-type/Heck reaction with allyloxy-tethered aryl iodides and aziridines. The strategy provides efficient access to benzannulated medium-sized rings via intermolecular cyclization. The substrate aryl iodide has two oxidative addition sites, that is, the aromatic C-I bond and the allyl-oxygen bond. The chemoselective oxidative addition of allyl-oxygen bonds is favored, followed by the activation of aromatic C-I bonds. Aziridine plays a key role. Mechanistic studies shed light on the reaction pathway.

Alkylation-Terminated Catellani Reactions by Cyclobutanol C-C Cleavage.

This report describes the first application of a cyclobutanol ring-opening procedure in the Catellani termination reaction, which includes two ß-carbon elimination processes. This tandem reaction features mild conditions, high yields, good functional group tolerance, and a broad substrate scope. Meanwhile, four types of electrophiles (N-benzoyloxyamines, alkyl iodides, aryl bromides, and benzyl chlorides) are quite compatible with this termination reaction for the construction of various types of polysubstituted aromatic hydrocarbons.

Palladium-catalyzed C-H glycosylation and retro Diels-Alder tandem reaction via structurally modified norbornadienes (smNBDs).

This report describes palladium-catalyzed C-H glycosylation and retro Diels-Alder tandem reaction via structurally modified norbornadienes (smNBDs). smNBDs were proposed to regulate the reactivity of the aryl-norbornadiene-palladacycle (ANP), including its high chemoselectivity and regioselectivity, which were the key to constructing C2 and C3 unsubstituted C4-glycosidic indoles. The scope of this substrate is extensive; the halogenated six-membered and five-membered glycosides were applied to the reaction smoothly, and N-alkyl (primary, secondary and tertiary) C4-glycosidic indoles can also be obtained by this method. In terms of mechanism, the key ANP intermediates characterized by X-ray single-crystal diffraction and further controlled experiments proved that the migration-insertion of smNBDs with phenylpalladium intermediate endows them with high chemo- and regioselectivity. Finally, density functional theory (DFT) calculation further verified the rationality of the mechanism.

Modular Synthesis of Aryl Thio/Selenoglycosides via the Catellani Strategy.

We described a novel palladium-catalyzed domino procedure for the preparation of (hetero)aryl thio/selenoglycosides. Readily available (hetero)aryl iodides and easily accessible 1-thiosugars/1-selenosugars are utilized as the substrates. Meanwhile, 10 types of sugars are quite compatible with this reaction with good regio- and stereoselectivity, high efficiency, and broad applicability (up to 89%, 53 examples). This method enables the straightforward formation of the C(sp2)-S/Se bond of (hetero)aryl thio/selenoglycosides.

Highly regioselective and stereoselective synthesis of C-Aryl glycosides via nickel-catalyzed ortho-C-H glycosylation of 8-aminoquinoline benzamides.

C-Aryl glycosides are of high value as drug candidates. Here a novel and cost-effective nickel catalyzed ortho-CAr-H glycosylation reaction with high regioselectivity and excellent α-selectivity is described. This method shows great functional group compatibility with various glycosides, showing its synthetic potential. Mechanistic studies indicate that C-H activation could be the rate-determining step.