Helvetica Chimica Acta最新文献

Supported metal hydrides are key reactive intermediates in various catalytic processes, such as hydrogenation and dehydrogenation, but are often challenging to characterize spectroscopically. Here, deuterium solid state nuclear magnetic resonance spectroscopy is used to understand the structure of the corresponding silica-supported zirconium hydrides after H/D exchange as an illustrative example of supported metal hydrides, which have been shown to display notable reactivity towards small molecules (e. g., CO₂ and N₂O) and to activate both C−H and C−C bonds, hence their use in to the conversion of hydrocarbons (alkanes, polyolefins etc.)

A practical, efficient approach for the synthesis of C4-arylated 2-quinolones from propargylic chlorides and anilines has been developed. The synthesis process involves subsequent oxidations of the initial products, tetrahydroquinolines and quinolinium ions, eventually leading to desired quinolones. A mechanism for the transformation is proposed based on a meticulous examination of intermediates and comprehensive control experiments. With a thorough understanding of the reaction mechanism, the applicability of the reaction scope is expanded.

Photoinduced direct α-alkylation reactions of ketones with arylalkenes using an organophotocatalyst and a Brønsted base were developed. It was found that the choice of both Brønsted base and photocatalyst was crucial, and in the presence of catalytic amounts of 2,4,6-tris(diphenylamino)-3,5-difluorobenzonitrile (3DPA2FBN) and LiO^tBu, the desired reactions of ketones with styrene analogues proceeded smoothly under blue-LED light irradiation to afford the products in moderate to high yields. This method constitutes an atom-economical alkylation process for α-functionalization of both cyclic and acyclic ketones.

Oxindoles are prevalent structures in natural products and pharmaceutically active molecules. To support structure–activity-relationship (SAR) studies in a medicinal chemistry program, we developed a straightforward and scalable synthesis route to 1-aminoethyl oxindole building blocks harboring various types of substituents. Our strategy relies on an intramolecular Buchwald–Hartwig amidation of a 2-bromophenylacetic amide precursor. The cyclization substrates can be prepared from readily available benzaldehydes by ortho-selective C(sp²)−H bromination followed by homologation to the corresponding phenylacetic acid derivatives. The process was optimized to allow for preparation of 246 g of one representative example.

Herein, we report four new chiral 1,4,7-triazacyclononane (TACN) derivatives and their corresponding nickel(II) chloride complexes. All TACN ligands are bearing one chiral N-substituent and two alkyl (methyl or tert-butyl) N-substituents, and we have developed a new synthetic method for the dimethyl-substituted TACN derivative, in order to prevent the rotational isomers that hinder the cyclization reaction. The nickel complexes change their coordination geometry significantly depending on the steric bulk of the N-alkyl substituents, from a dinuclear tris(μ-chloro)dinickel complex to mononuclear Ni-dichloride and Ni-chloride complexes. These complexes were then employed in the alkyl-alkyl Kumada cross-coupling reaction and revealed that the more sterically hindered ligands produced more homocoupled product rather than the cross-coupled product, while the mononuclear Ni-dichloride complex exhibited significantly lower catalytic activity. These chiral complexes were also employed in enantioconvergent cross-coupling reactions as well, to afford significant enantioenrichment. Overall, the least sterically hindered Ni complex yields the best yields in the alkyl-alkyl Kumada cross-coupling reaction among the four complexes investigated, as well as the highest enantioselectivity.

In order to expand the knowledge on linear alicyclic musks, a set of 29 small-ring (racemic) analogues of the biodegradable and renewable alicyclic musk Romandolide was designed, prepared, and evaluated. The common short and modular synthesis employs either commercially available or easily accessible (substituted) cyclopropyl/cyclobutyl ketones and acids. These were transformed in three/four steps to the target compounds. Their qualitative olfactory analysis reveals that contraction of cyclohexane ring of Romandolide to smaller rings annihilates the genuine musk scent, though many of these share the metallic hot-iron off-note of some macrocyclic musks. Indeed, these new derivatives exhibit a plethora of pleasant, interesting, and potentially useful scents including herbal, green, fruity, or chocolate ones accompanied by various undertones. The powdery, fruity ionone odor of the dimethyl cyclobutyl compound was found to be most interesting as it possesses a very natural raspberry and violet character. Computational modelling suggest that the lowest-energy conformers of the target compounds do either not adopt a true U-shape as was speculated to be a prerequisite for a musk odor, or that the quaternary carbon atom of the dimethyl-substituted cyclobutane is not well placed to fit into a hydrophobic binding pocket on the corresponding receptor site.

Keap1 is associated with cytoprotective signaling. These roles of Keap1 typically focus on its role as a degrader of the antioxidant response (AR) transcription factor, Nrf2, and the inhibition of this process upon Keap1 labeling by electrophiles. However, work from several laboratories has reemphasized both the important role of Nrf2 binding in negatively regulating AR, and the fact that electrophile Keap1 modification dissociates Nrf2 from Keap1. This model appears to be applicable to other signaling modes regulated by Keap1. Here, we use recent data we have derived using experiments in zebrafish and cultured cells to discuss different models of Keap1 regulation.

DNA biosensors are promising candidates for the development of point-of-care diagnosis methods. They can be inserted in microfluidic platforms, are often non-expensive, and can be produced for a variety of targeted analytes. However, their development faces several challenges, some of which arise from their surface design. Among the characteristics which affect the binding efficiency of DNA probes to their targeted genes, the packing density and lateral spacing of the probe sequences must be controlled to provide enough binding sites and avoid crowding effect. It has also been demonstrated that increasing the space between the probe and the substrate can enhance the sensitivity of the sensing surface. Herein, we describe a methodology to control the vertical distance between DNA probes and a glass support, and lateral spacing between the probes. Such functionalization strategy could help the development of sensing surface with high hybridization density, and therefore high sensitivity.

Research towards the development of novel synthetic methods to access substituted bicyclo[1.1.1]pentane (BCP) structural motifs has been conducted by both academic groups and industrial organizations. Recent developments have been strongly focused on the utility of visible light catalysis to promote a cornucopia of radical-based transformations, including incorporation of BCP motifs. While these methods have proven powerful in accessing various substitution patterns, some scalability challenges remain. Herein we describe a focused effort on the high-throughput experimentation (HTE) guided optimization of a decarboxylative non-photonic coupling that can be conducted using traditional batch reactors. Employing an unanticipated mixture of copper(I) chloride and cyclopentyl methyl ether (CPME) results in the formation of a N-substituted bicyclo[1.1.1]pentyl pyrazole product while limiting the overall equivalency of the hypervalent iodonium precursor.