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.

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.

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.

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.

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.

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.

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.

Phosphine-catalysed α-umpolung addition of nucleophiles to δ-acetoxy allenoates: stereoselective synthesis of 2,4-dienoates.

The first example of phosphine-catalyzed α-umpolung addition of nucleophiles to allenoates is described, which features the use of δ-acetoxy allenoate to generate a 3-phosphonium-2,4-dienoate intermediate, thus facilitating the α-umpolung addition of nucleophiles. Both sulfinate and diarylphosphine oxide are competitive nucleophiles, affording highly activated conjugated dienes with good to excellent stereoselectivities.

Pd(0)-Catalysed asymmetric reductive Heck-type cyclization of (Z)-1-iodo-1,6-dienes and enantioselective synthesis of quaternary tetrahydropyridines.

A Pd(0)/(S)-p-MeO-BnPHOX catalytic system has been established for the asymmetric reductive Heck reaction of (Z)-1-iodo-1,6-dienes, which affords quaternary tetrahydropyridines with good to excellent enantioselectivities. This reaction tolerates a wide range of substituted alkene moieties, including 1,1-disubstituted, 1,1,2-trisubstituted as well as 1,2-disubstituted alkenes.

Construction of polycyclic frameworks via a DMAP-catalysed tandem addition-(4 + 2) annulation sequence of δ-acetoxy allenoate.

Here is reported the DMAP-catalyzed addition/(4 + 2) annulation domino reaction of δ-acetoxy allenoate with either salicylaldehyde-derived oxadiene or pyrrolealdehyde-derived oxadiene, which provides a facile method toward polycyclic frameworks. A cationic intermediate, 3-ammonium-2,4-dienoate, is proposed to be involved via an addition-elimination process between an allenoate and a catalyst, which is capable of undergoing addition with either O- or N-nucleophile and subsequent (4 + 2) annulation with oxadiene.

Amine-Catalyzed Asymmetric (3 + 3) Annulations of ß'-Acetoxy Allenoates: Enantioselective Synthesis of 4H-Pyrans.

The asymmetric (3 + 3) annulations of ß'-acetoxy allenoates with either 3-oxo-nitriles or pyrazolones have been realized by using 6'-deoxy-6'-[(l)-N,N-(2,2'-oxidiethyl)-valine amido]quinine (6h) as the catalyst. The three functions of catalyst 6h, including Lewis base (quinuclidine N), H-bond donor (amide NH), and Brønsted base (morpholine N), cooperatively take crucial roles on the chemo- and enantioselectivity, allowing for the construction of 4H-pyran and 4H-pyrano[2,3-c]pyrazole in high yields and enantioselectivity.

Rh(I) -Catalyzed Cyclizative Addition Reaction of 1,6-Enyne and Sulfonyl Chloride by Carbophilic Activation.

The π-acid-catalyzed cyclizations of 1,n-enynes by carbophilic activation have been extensively studied and appear as highly attractive processes, yet the cases within a catalytic cycle based on redox principle are rare. Herein, we report the cyclizative addition reactions of 1,6-enynes and sulfonyl chlorides by using a [Rh(cod)Cl/dppf] (dppf=1,1'-bis(diphenylphosphino)ferrocene) catalyst system. The process features the involvement of oxidative addition of sulfonyl chloride to Rh(I) catalyst, which generates [(dppf)(RSO2 )RhCl2 ] as a π-acid species to trigger cyclizative addition in a 6-endo-dig manner by carbophilic activation. Moreover, the catalytic protocol is also applicable to 1,6-diene analogues.

Phosphine-Catalyzed Addition/Cycloaddition Domino Reactions of ß'-Acetoxy Allenoate: Highly Stereoselective Access to 2-Oxabicyclo[3.3.1]nonane and Cyclopenta[a]pyrrolizine.

Two classes of phosphine-catalyzed addition/cycloaddition domino reactions of ß'-acetoxy allenoate 1 have been developed. The reaction of 1 with 2-acyl-3-methyl-acrylonitrile 2 readily occurs to give 2-oxabicyclo[3.3.1]nonane 3, furnishing the ß'-addition/[4 + 4] cycloaddition domino sequence. In this sequence, ß'C of allenoate 1 is an electrophilic center, and its ß'C and γC serve as a 1,4-dipole. When the other reaction partner is switched to 2-acyl-3-(2-pyrrole)-acrylonitrile 8, a γ-addition/[3 + 2] cycloaddition domino reaction is instead observed, in which allenoate 1 exhibits dual electrophilic reactivity of γC and 1,3-dipole chemical behavior of ßC and ß'C. Furthermore, both of these two asymmetric variants have also been achieved with up to 93% ee. The domino reactions presented in this report are valuable for highly stereoselective construction of complex structures under mild reaction conditions.

Shape-Dependent Activity of Ceria for Hydrogen Electro-Oxidation in Reduced-Temperature Solid Oxide Fuel Cells.

Single crystalline ceria nanooctahedra, nanocubes, and nanorods are hydrothermally synthesized, colloidally impregnated into the porous La0.9Sr0.1Ga0.8Mg0.2O3-δ (LSGM) scaffolds, and electrochemically evaluated as the anode catalysts for reduced temperature solid oxide fuel cells (SOFCs). Well-defined surface terminations are confirmed by the high-resolution transmission electron microscopy--(111) for nanooctahedra, (100) for nanocubes, and both (110) and (100) for nanorods. Temperature-programmed reduction in H2 shows the highest reducibility for nanorods, followed sequentially by nanocubes and nanooctahedra. Measurements of the anode polarization resistances and the fuel cell power densities reveal different orders of activity of ceria nanocrystals at high and low temperatures for hydrogen electro-oxidation, i.e., nanorods > nanocubes > nanooctahedra at T ≤ 450 °C and nanooctahedra > nanorods > nanocubes at T ≥ 500 °C. Such shape-dependent activities of these ceria nanocrystals have been correlated to their difference in the local structure distortions and thus in the reducibility. These findings will open up a new strategy for design of advanced catalysts for reduced-temperature SOFCs by elaborately engineering the shape of nanocrystals and thus selectively exposing the crystal facets.

Palladium(0)-catalyzed iminohalogenation of alkenes: synthesis of 2-halomethyl dihydropyrroles and mechanistic insights into the alkyl halide bond formation.

Although the advances on carbon halide reductive elimination have been made, the alkyl bromide and chloride analogues remain a challenge. Here, a palladium(0)-catalyzed iminohalogenation of γ,δ-unsaturated oxime esters is described, and the use of electron-poor phosphine ligands proved to be crucial to promoting alkyl bromide and chloride reductive elimination. Furthermore, S(N)2-type alkyl bromide and chloride reductive elimination has also been established.

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.

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.

Antibody responses to respiratory syncytial virus: a population-based cross-sectional serological study in Southern China, 2021.

OBJECTIVES: With remarkable progress in the field of respiratory syncytial virus (RSV) prophylaxis, it is critical to understand population immunity against RSV. We aim to describe the RSV pre-F IgG antibodies across all age groups in Southern China and to evaluate the risk factors associated with lower antibody levels. METHODS: We performed a community-based cross-sectional sero-epidemiological study in Anhua County, Hunan Province, Southern China, from July 15, 2021, to November 5, 2021. Serum samples were tested for IgG antibodies against the RSV prefusion F (pre-F) protein using an enzyme-linked immunosorbent assay. We estimated the geometric mean titres (GMTs) and seropositivity rates across all age groups. The generalized linear models were built to identify factors associated with antibody levels. RESULTS: A total of 890 participants aged 4 months to older than 89 years were enrolled. The lowest RSV pre-F IgG GMTs were observed in infants and toddlers aged 4 months to younger than 2 years (3.0; 95% CI, 2.6-3.5). With increasing age, the RSV pre-F IgG GMT increased to 4.3 (95% CI, 4.1-4.4) between the ages of 2 and younger than 5 years and then stabilized at high levels throughout life. All the children had serological evidence of RSV infection by the age of 5 years. Age was associated with RSV pre-F antibody levels in children, with an estimated 1.8-fold (95% CI, 1.1-2.9) increase in titre per year before 5 years of age, although it was not significantly associated with antibody levels in adults aged older than 60 years. DISCUSSION: Our findings could provide a comprehensive understanding of the gaps in RSV immunity at the population level and inform the prioritization of immunization platforms.