Helvetica Chimica Acta最新文献

The selective reduction of ketones to the corresponding hydrocarbons is a fundamental transformation in organic synthesis with applications ranging from pharmaceuticals to biomass valorization. Traditional methods such as the Wolff–Kishner and Clemmensen reductions often face scalability challenges due to the use of harsh conditions and stoichiometric, often toxic reagents. Here, we report that bimetallic Ir-Mo supported on SiO₂ is a highly efficient catalyst for the hydrodeoxygenation (HDO) of ketones using dihydrogen as a reductant, generating water as a sole byproduct. The catalyst, prepared from grafting Ir(COD)(DIA) (COD = 1,5-cyclooctadiene, DIA = N,N’-diisopropylacetamidinate) on a Mo-doped SiO₂ support followed by reduction under H₂, forms alloyed nanoparticles (2.0 nm) that exhibit very high selectivity for the deoxygenation of acetophenone derivatives, aliphatic ketones, and α-ketoesters. The observed ring-opening of cyclopropyl phenyl ketone and the formation of dimeric side products via carbonyl-carbon coupling in acetophenones suggest the involvement of carbon-centred radical intermediates. Overall, this work complements conventional methods, providing a more sustainable and versatile approach to ketone reduction in synthetic application.

Donor-acceptor (DA) cyclobutanes are emerging as valuable synthetic intermediates due to their ring strain and polarized C─C bonds, which allow for 1,4-dipolar reactions. This review highlights recent advances in DA cyclobutane reactivity, particularly (4+2) annulation reactions used to construct six-membered rings. It discusses the development of annulations involving carbon-, oxygen-, and nitrogen-based donor groups, initiated by Lewis acid catalysis, Brønsted acid, and electrocatalysis. Additionally, enantioselective transformations and the challenges associated with diester acceptor motifs and their replacement with monoester groups are presented. Overall, this review provides a comprehensive overview of annulation reactions with donor-acceptor cyclobutanes and emphasizes their potential in stereoselective syntheses of functionalized carbo- and hetero-cycles embedded in complex natural product frameworks.

Supramolecular polymers based on electron-deficient n-type organic semiconductors are promising candidates for organic electronic applications. Hexaazatrinaphthylene (HATNA) is particularly attractive due to its high charge-carrier mobility and redox activity. However, the impact of molecular symmetry on its supramolecular polymerization remains underexplored. Here, we compare two constitutional isomers of amide-functionalized HATNA derivatives: a C₃-symmetric (C₃-HATNA) and a C₁-symmetric (C₁-HATNA) variant. Although both isomers exhibit similar electrochemical and optical properties in solution, their supramolecular polymerization leads to markedly different structural organizations. Spectroscopic, microscopic, scattering, and computational studies reveal that C₃-HATNA forms tightly packed assemblies, consistent with stronger and more directional hydrogen bonding. In contrast, the reduced symmetry of C₁-HATNA leads to less directional hydrogen bonding and asymmetric solvent exposure of the core, promoting bundling and the formation of longer fibers. These findings highlight the role of molecular symmetry in directing assembly pathways and provide insights for designing supramolecular materials for organic electronics.

Glycine derivatives represent a class of important molecules whose structural motifs are commonly present in pharmaceutical compounds. N-H functionalization of ester-containing diazo compounds constitutes an effective strategy for the synthesis of glycine derivatives. For X-H (X = N, O, S, etc.) functionalization of diazo compounds, the most prevalent pathway proceeds via carbene intermediates, although a small number of cases involve cationic intermediates. However, versatile dicationic intermediates derived from α-diazo sulfonium salts have rarely been reported. In this study, a three-component bisnucleophilic substitution reaction for the synthesis of glycine derivatives has been developed. Amines were employed as nucleophiles to undergo controlled N-H/C-H functionalization with α-diazo sulfonium salt via a dicationic intermediate. The nucleophilic amines can be selectively utilized as either carbon-centered or nitrogen-centered nucleophiles. Furthermore, product transformation studies further demonstrate the synthetic utility of this method.

Cyclic acrylates are an under-explored class of electrophile for conjugate addition reactions with aromatic boronic acids. In order to supply a range of saturated heterocycles for medicinal chemistry hit optimization, plate-based parallel screening enabled the discovery of a rhodium-catalyzed 1,4-conjugate addition using Hayashi ligand. Scope exploration included variation in the cyclic acrylate ring size (pyrrolidine, piperidine, azepane), the choice of N-protection group (CBz, Boc, and other carbamates) and the range of boronic acid nucleophiles, amongst other parameters. The influence of these parameters on yield and enantioselectivity is described. The step was then established into a 3-step sequence consisting of: asymmetric conjugate addition; base-mediated epimerization to the trans diastereoisomer; and borohydride reduction of the ester to the alcohol building block. Multi-gram deliveries of complex sp3-rich enantio- and diastereo-meric building blocks could thereby be established.

We report the formation of tetrazolidinones and thiatetrazolidines, i.e., heterocycles with four σ-bonded nitrogen atoms in their structure, via the oxidative coupling of two hydrazines tethered by a carbonyl or a sulfonyl moiety. Different strategies for installing the tethers on the various bishydrazine precursors are first presented, and their cyclization is presented next. The influence of the protecting groups on the α and/or β nitrogen atoms, as well as the nature of the oxidant leading to the tetrazane core, is studied.

Pyrrole is recognized as a critical component in various natural molecules and bioactive products, making it a focal point in organic synthesis. In this study, we report a novel photoredox strategy that leverages visible light to catalyze the synthesis of tetra-C-substituted pyrrole derivatives from enamines, employing acridine and a cobaloxime as catalysts. This method offers significant advantages, including the elimination of external oxidants and the capability to conduct reactions under mild conditions, thereby expanding the range of viable pyrrole derivatives while maintaining functional group compatibility. Mechanism investigations demonstrated that radical species were involved in the process and light irradiation was essential for the efficient transformation.

Infectious diseases pose a significant threat to global healthcare, especially with the rapid emergence of antimicrobial resistance and limited development of antimicrobials. Hence, the search for new and effective antimicrobial is paramount. Benzimidazole represents a unique, aromatic heterocycle with broad spectrum of biological applications. The present study aimed to evaluate the antibacterial and antifungal activities, and molecular docking studies of N1-substituted 5-alkylsulfonyl benzimidazole derivatives (23–36) synthesized in our previous work. The compounds were tested for their in vitro antimicrobial activity against diverse strains of Gram-positive and Gram-negative bacteria, and fungal species using the microdilution assay. In silico docking analysis of the most promising compounds was also investigated against DNAGyr and DHFR targets to simulate the ligand-receptor interaction. Compound 26, bearing cyclohexyl and 3,4-difluorophenyl moieties at the N1 and C2 positions of the benzimidazole ring, respectively displayed the most potent antibacterial activity against E. faecalis (MIC = 12.5 µg/mL), and the most potent antifungal activity (MIC = 16 µg/mL) against Candida albicans and Candida parapsilosis. The molecular docking analysis provided useful insights into the interaction of the molecules with key amino acid residues. This compound provides useful lead for the development of novel antibacterial and antifungal agent against susceptible organisms.

Dynamic covalent chemistry involving conjugate addition requires reversibility under specific conditions. In classical systems, reversible Michael addition of thiols is achieved using α-cyano acrylamides. The more recent oxSTEF reagents introduce β,β-bissulf(ox)ido enones instead to achieve reversibility of conjugate addition. The objective of this study was to investigate the activity of oxSTEF reagents in the context of thiol-mediated uptake (TMU) into cells, in comparison as well as in combination with conventional reversible Michael acceptors. Whereas none of tested oxSTEF reagents enables or inhibits TMU significantly, some activate the TMU of conventional α-cyano acrylamides (cyclic β-sulfido-β-sulfoxido enones), and others activate TMU of α-helical thioredoxin mimics through intriguing and selective tetrel-centered dynamic covalent exchange cascades. Activated by an unorthodox oxSTEF Michael acceptor, classical reversible Michael acceptors emerge as the most active monomeric TMU probes known today.

1,3-Dialkyltriazenides are isolobal to amidinates, and both ligands are popular in atomic layer deposition. Given our recent success with the N,N’-diisopropylacetamidinate (DIA) ligand in surface organometallic chemistry, we investigated the 1,3-tert-butyltriazenide (DTZ) ligand to stabilize Ni- and Pd-allyl complexes for the generation of supported nanoparticles. Using the analogous synthetic pathway employed for allyl-amidinate complexes, the formation of dinuclear structures was obtained, where two triazenide ligands bridge the metal centers. Grafting on SiO_2-700 was almost quantitative for {Ni(η³-allyl)(µ-DTZ)}₂ while only partial for {Pd(η³-allyl)(µ-DTZ)}₂ (ca. 50%), contrasting what was observed for the corresponding amidinate derivatives that grafted almost quantitatively for both Ni and Pd. Heat treatment of the grafted materials under a flow of H₂ yielded supported nanoparticles (Ni: 1.1 nm, Pd: 1.3 nm) that were significantly smaller than those obtained with the respective amidinate complexes and feature very narrow size distribution (standard deviation σ = 0.2 nm for Ni, 0.3 nm for Pd). Hence, the presented complexes are viable precursors for the generation of small and narrowly dispersed supported nanoparticles.