Atroposelective synthesis of axially chiral biaryls by palladium‐catalyzed C−H olefination, using tert‐leucine as an inexpensive, catalytic, and transient chiral auxiliary, has been realized. This ...strategy provides a highly efficient and straightforward access to a broad range of enantioenriched biaryls in good yields (up to 98 %) with excellent enantioselectivities (95 to >99 % ee). Kinetic resolution of trisubstituted biaryls bearing sterically more demanding substituents is also operative, thus furnishing the optically active olefinated products with excellent selectivity (95 to >99 % ee, s‐factor up to 600).
No attachements: The title reaction employs tert‐leucine as a transient chiral auxiliary and provides efficient access to enantioenriched biaryls in good yields (up to 98 %) with excellent enantioselectivities (up to >99 % ee). Kinetic resolution of trisubstituted biaryls bearing sterically more demanding substituents is also operative, thus furnishing the optically active olefinated products with excellent selectivity (up to >99 % ee, s‐factor up to 600).
The site‐selective functionalization of unactivated C(sp3)−H bonds remains one of the greatest challenges in organic synthesis. Herein, we report on the site‐selective δ‐C(sp3)−H alkylation of amino ...acids and peptides with maleimides via a kinetically less favored six‐membered palladacycle in the presence of more accessible γ‐C(sp3)−H bonds. Experimental studies revealed that C−H bond cleavage occurs reversibly and preferentially at γ‐methyl over δ‐methyl C−H bonds while the subsequent alkylation proceeds exclusively at the six‐membered palladacycle that is generated by δ‐C−H activation. The selectivity can be explained by the Curtin–Hammett principle. The exceptional compatibility of this alkylation with various oligopeptides renders this procedure valuable for late‐stage peptide modifications. Notably, this process is also the first palladium(II)‐catalyzed Michael‐type alkylation reaction that proceeds through C(sp3)−H activation.
The site‐selective δ‐C(sp3)−H alkylation of amino acids and peptides with maleimides is enabled by a palladium catalyst. C−H bond cleavage occurs reversibly and preferentially at γ‐methyl over δ‐methyl C−H bonds while the subsequent alkylation proceeds exclusively at the six‐membered palladacycle generated by δ‐C−H activation. The selectivity can be explained by the Curtin–Hammett principle. PA=picolinamide.
The discovery of proper ligands to simultaneously modulate the reactivity and effectively control the stereoselectivity is a central topic in the field of enantioselective C−H activation. Herein, we ...reported the synthesis of axially chiral biaryls by Pd‐catalyzed atroposelective C−H olefination. A novel chiral spiro phosphoric acid, STRIP, was identified as a superior ligand for this transformation. A broad range of axially chiral quinoline derivatives were synthesized in good yields with excellent enantioselectivities (up to 98 % ee). Density functional theory was used to gain a theoretical understanding of the enantioselectivities in this reaction.
The discovery of proper ligands to simultaneously modulate the reactivity and effectively control the stereoselectivity is a central topic in the field of enantioselective C−H activation. Herein, the synthesis of axially chiral biaryls by Pd‐catalyzed atroposelective C−H olefination is reported. A broad range of axially chiral quinoline derivatives were synthesized in good yields with excellent enantioselectivities (up to 98 % ee).
Since the emergence of the concept of chemical topology, interlocked molecular assemblies have graduated from academic curiosities and poorly defined species to become synthetic realities. ...Coordination-directed synthesis provides powerful, diverse, and increasingly sophisticated protocols for accessing interlocked molecules. Originally, metal ions were employed solely as templates to gather and position building blocks in entwined or threaded arrangements. Recently, metal centers have increasingly featured within the backbones of the integral structural elements, which in turn use noncovalent interactions to self-assemble into intricate topologies. By outlining ingenious recent examples as well as seminal classic cases, this Review focuses on the role of metal–ligand paradigms in assembling molecular links. In addition, the ever-evolving approaches to efficient assembly, the structural features of the resulting architectures, and their prospects for the future are also presented.
AbstractThe instability of structural members under axial compression most likely causes spatial structural collapse. Therefore, the configuration of double-layer members (DLMs) is proposed in this ...study to improve the stability of compression members. Experiments on four specimens (two single-layer members and two DLMs) were conducted, where the failure mechanism was revealed based on analysis of a validated finite-element (FE) model. Parametric studies were also performed to investigate the effects of different parameters on the compressive mechanical behaviors of the DLMs. Results showed that the desired failure mode of the DLMs was high-order buckling with torsion of the inner tube and no global buckling failure prior to contact between the outer tube and end plate (HTCG). Under the failure mode of HTCG, the ultimate load and ductility were greatly improved due to the constraint of the outer tube. Finally, predictions of the crucial loads derived from the equilibrium differential equation and empirical formula were in good agreement with the test and FE results.
A new label‐free sensing mechanism is demonstrated experimentally by monitoring the whispering‐gallery mode broadening in microcavities. It is immune to both noise from the probe laser and ...environmental disturbances, and is able to remove the strict requirement for ultra‐high‐Q mode cavities for sensitive nanoparticle detection. This ability to sense nanoscale objects and biological analytes is particularly crucial for wide applications.
Ribosomally synthesized and post‐translationally modified peptides (RiPPs) are a fascinating group of natural products that exhibit diverse structural features and bioactivities. P450‐catalyzed RiPPs ...stand out as a unique but underexplored family. Herein, we introduce a rule‐based genome mining strategy that harnesses the intrinsic biosynthetic principles of RiPPs, including the co‐occurrence and co‐conservation of precursors and P450s and interactions between them, successfully facilitating the identification of diverse P450‐catalyzed RiPPs. Intensive BGC characterization revealed four new P450s, KstB, ScnB, MciB, and SgrB, that can catalyze the formation of Trp‐Trp‐Tyr (one C−C and two C−N bonds), Tyr‐Trp (C−C bond), Trp‐Trp (C−N bond), and His‐His (ether bond) crosslinks, respectively, within three or four residues. KstB, ScnB, and MciB could accept non‐native precursors, suggesting they could be promising starting templates for bioengineering to construct macrocycles. Our study highlights the potential of P450s to expand the chemical diversity of strained macrocyclic peptides and the range of biocatalytic tools available for peptide macrocyclization.
P450 enzymes are highly effective catalysts, yet little research has been conducted on their ability to modify ribosomal peptides. Now uncharted bacterial cytochrome P450s responsible for the macrocyclization of ribosomal peptides have been discovered by sequence‐ and 3D‐structure‐based genome mining. These P450s exhibit diverse catalytic capabilities, catalyzing aromatic crosslinking by forming C−C, C−N, and C−O bonds.
The methods for the cross‐coupling of aryl(trialkyl)silanes are long‐standing challenges due to the extreme inertness of C−Si(R3) bond, though the reaction is environmentally friendly and highly ...regioselective to synthesize biaryls. Herein, we report a copper‐catalyzed cross‐coupling of aryl(trialkyl)silanes and aryl via a radical mechanism. The reaction proceeds efficiently with aryl sulfonium salts as limiting reagents, exhibits broad substrate scope, and provides an important synthetic strategy to acquire biaryls, exemplified by unsymmetrical fluorescence probes and late‐stage functionalization of drugs. Of note, the experimental and theoretical mechanistic studies revealed a radical mechanism where the copper catalyst and CsF play critical roles on the radical generation and desilylation process.
The aryl radical from sulfonium salts have been generated through copper‐metal‐catalyzed processes, which enable the successful biaryl transformation through the addition to the aryl(trialkyl)silanes for the first time. Given the fast development in the copper catalysis, this method is expected to present new opportunities for exploring aryl(trialkyl)silanes in biaryl synthesis.
Chirality is one of the key factors affecting the medicinal efficacy of compounds. In addition to central chirality, sterically hindered chiral axes commonly appear in drugs and the resulting ...chirality is known as atropisomerism. With developments in medicinal chemistry, atropisomerism has attracted increasing attention. This review discusses the classification, biological activity, pharmacokinetics, toxicity and side effects of atropisomers, and can serve as a reference in the research and development of potential chiral drugs.
We are experiencing a historical moment with an unprecedented challenge of the COVID-19 global pandemic. The outbreak of COVID-19 will have a long-term and profound impact on older adults' health and ...well-being. Social isolation and loneliness are likely to be one of the most affected health outcomes. Social isolation and loneliness are major risk factors that have been linked with poor physical and mental health status. This paper discusses several approaches that may address the issues of social isolation and loneliness. These approaches include promoting social connection as public health messaging, mobilizing the resources from family members, community-based networks and resources, developing innovative technology-based interventions to improve social connections, and engaging the health care system to begin the process of developing methods to identify social isolation and loneliness in health care settings.
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