Enantioselective Aminosilylation of Alkenes by Palladium/Ming-Phos-Catalyzed Tandem Narasaka-Heck/Silylation Reaction.

A Pd-catalyzed enantioselective aminosilylation of alkenes via tandem Aza-Heck/silylation reaction under Pd/Sadphos catalysis is disclosed. A wide array of oxime esters and silicon reagents are tolerated, furnishing the chiral pyrrolines bearing one quaternary or two contiguous stereocenters in good yield with high enantioselectivity. Not only terminal alkenes but also tri-substituented internal alkenes successfully participate in the reaction, delivering vicinal stereocenters in complete diastereoselectivity and high enantioselectivity. DFT study is conducted to probe the reaction pathway and the origin of the enantioselectivity, which revealed that the stereoinduction arises from the weak interaction between the aromatic ring of the substrate fragment and naphthyl group in the ligand.

Personal exposure to airborne organic pollutants and lung function changes among healthy older adults.

Epidemiological evidence on the impact of airborne organic pollutants on lung function among the elderly is limited, and their underlying biological mechanisms remain largely unexplored. Herein, a longitudinal panel study was conducted in Jinan, Shandong Province, China, involving 76 healthy older adults monitored over a span of five months repetitively. We systematically evaluated personal exposure to a diverse range of airborne organic pollutants using a wearable passive sampler and their effects on lung function. Participants' pulmonary function indicators were assessed, complemented by comprehensive multi-omics analyses of blood and urine samples. Leveraging the power of interaction analysis, causal inference test (CIT), and integrative pathway analysis (IPA), we explored intricate relationships between specific organic pollutants, biomolecules, and lung function deterioration, elucidating the biological mechanisms underpinning the adverse impacts of these pollutants. We observed that bis (2-chloro-1-methylethyl) ether (BCIE) was significantly associated with negative changes in the forced vital capacity (FVC), with glycerolipids mitigating this adverse effect. Additionally, 31 canonical pathways [e.g., high mobility group box 1 (HMGB1) signaling, phosphatidylinositol 3-kinase (PI3K)/AKT pathway, epithelial mesenchymal transition, and heme and nicotinamide adenine dinucleotide (NAD) biosynthesis] were identified as potential mechanisms. These findings may hold significant implications for developing effective strategies to prevent and mitigate respiratory health risks arising from exposure to such airborne pollutants. However, due to certain limitations of the study, our results should be interpreted with caution.

Associations of environmental cadmium exposure with kidney damage: Exploring mediating DNA methylation sites in Chinese adults.

Environmental exposure is widely recognized as the primary sources of Cadmium (Cd) in the human body, and exposure to Cd is associated with kidney damage in adults. Nevertheless, the role of DNA methylation in Cd-induced kidney damage remains unclear. This study aimed to investigate the epigenome-wide association of environmental Cd-related DNA methylation changes with kidney damage. We included 300 non-smoking adults from the China in 2019. DNA methylation profiles were measured with Illumina Infinium MethylationEPIC BeadChip array. Linear mixed-effect model was employed to estimate the effects of urinary Cd with DNA methylation. Differentially methylated positions (DMPs) associated with urinary Cd were then tested for the association with kidney damage indicators. The mediation analysis was further applied to explore the potential DNA methylation based mediators. The prediction model was developed using a logistic regression model, and used 1000 bootstrap resampling for the internal validation. We identified 27 Cd-related DMPs mapped to 20 genes after the adjustment of false-discovery-rate for multiple testing among non-smoking adults. 17 DMPs were found to be associated with both urinary Cd and kidney damage, and 14 of these DMPs were newly identified within the Chinese. Mediation analysis revealed that DNA methylation of cg26907612 and cg16848624 mediated the Cd-related reduced kidney damage. In addition, ten variables were selected using the LASSO regression analysis and were utilized to develop the prediction model. It found that the nomogram model predicted the risk of kidney damage caused by environmental Cd with a corrected C-index of 0.779. Our findings revealed novel DMPs associated with both environmental Cd exposure and kidney damage among non-smoking adults, and developed an easy-to-use nomogram-illustrated model using these novel DMPs. These findings could provide a theoretical basis for formulating prevention and control strategies for kidney damage from the perspective of environmental pollution and epigenetic regulation.

Pd/Ming-Phos-Catalyzed Asymmetric Three-Component Arylsilylation of N-Sulfonylhydrazones: Enantioselective Synthesis of gem-Diarylmethine Silanes.

A Pd-catalyzed enantioselective three-component reaction of N-sulfonylhydrazones, aryl bromides, and silylboronic esters is developed, enabling the synthesis of chiral gem-diarylmethine silanes in high enantioselectivity with the use of a newly identified Ming-Phos. Compared with N-tosyl, the more easily decomposed N-mesitylsulfonyl is more suitable as the masking group of electron-rich hydrazone to improve the reaction efficiency. The reaction features a broad scope concerning both coupling partners, high enantioselectivity, and mild reaction conditions. The ready access to enantiomers and utility of this catalytic method are also presented.

Catalytic Enantioselective Reductive Cross Coupling of Electron-Deficient Olefins.

We report an enantioselective reductive cross coupling of electron-deficient olefins. Using a visible-light-driven cooperative photoredox and chiral Brønsted acid-catalyzed reaction with a Hantzsch ester as the terminal reductant, various cyclic and acyclic enones with 2-vinylpyridines were converted in high yields (up to 93%) to a wide range of enantioenriched pyridine derivatives featuring diverse γ-tertiary carbon stereocenters with good to excellent enantioselectivities (up to >99% ee).

Palladium-Catalyzed Asymmetric Cross-Coupling Reactions of Cyclobutanols and Unactivated Olefins.

Transition-metal-catalyzed activations of carbon-carbons bonds of small strained rings have widespread applications in synthetic and medicinal chemistry. However, coupling reactions of cyclobutanols involving ß-carbon elimination to construct C(sp3)-C(sp3) bonds have scarcely been developed. Here, we demonstrate a highly enantioselective Pd-catalyzed intermolecular C(sp3)-C(sp3) coupling reaction of a broad range of cyclobutanol derivatives and unactivated alkenes, allowing convenient access to a series of chiral benzene-fused cyclic compounds in a highly regio-, chemo-, and enantioselective manner.

Catalytic Enantioselective Addition of Prochiral Radicals to Vinylpyridines.

Pyridine, one of the most important azaarenes, is ubiquitous in functional molecules. The electronic properties of pyridine have been exploited to trigger asymmetric transformations of prochiral species as a direct approach for accessing chiral pyridine derivatives. However, the full potential of this synthetic strategy for the construction of enantioenriched γ-functionalized pyridines remains untapped. Here, we describe the first enantioselective addition of prochiral radicals to vinylpyridines under cooperative photoredox and asymmetric catalysis mediated by visible light. The enantioselective reductive couplings of vinylpyridines with aldehydes, ketones, and imines were achieved by employing a chiral Brønsted acid to activate the reaction partners and provide stereocontrol via H-bonding interactions. Valuable chiral γ-secondary/tertiary hydroxyl- and amino-substituted pyridines were obtained in high yields with good to excellent enantioselectivities.