European Journal of Organic Chemistry最新文献

The Front Cover shows a calm night sky filled with molecular constellations—gem-difluorinated fused bicyclic amines. At the center, a radiant CF₂ fragment with a glowing halo symbolizes its strong influence on the compound’s properties (basicity and lipophilicity). Building silhouettes represent places from all over Ukraine that have some special significance to the authors. Labels on the buildings indicate the key methods used for the compound physicochemical characterization. More information can be found in the Research Article by O. O. Grygorenko and co-workers (DOI: 10.1002/ejoc.202500728). Cover design by O. S. Liashuk.

We describe a hexafluoroisopropanol (HFIP)-promoted epoxide ring-opening cyclization of readily accessible 2-[(2-substituted-1-naphthyloxy)methyl]-3-aryloxiranes, proceeding via a regioselective 7-endo cyclization at the peri (C8) position of the naphthalene ring. This transformation provides a new class of naphtho[1,8-bc]oxepine derivatives with complete regio- and diastereoselectivity. The C2 substituent on the naphthalene framework, along with the π-activating aryl group on the epoxide, plays a pivotal role in enabling the reaction. The method operates under mild conditions, tolerates a broad substrate scope, and is readily amenable to gram-scale synthesis. Moreover, the versatility of this strategy is underscored by its successful extension to the diastereoselective synthesis of oxepino[4,3,2-cd]indoles.

Herein, we report an efficient and scalable synthesis of the core skeleton of elacestrant, a selective estrogen receptor degrader used in breast cancer treatment. The present synthesis features simple synthetic transformations, involving one-pot conversion of 6-hydroxy-1-tetralone into a cyclic olefin followed by copper-catalyzed arylation of the cyclic olefin (iodometathesis) with a diaryliodonium salt as a key strategy to achieve the core skeleton on a gram scale. This procedure was extended to the total synthesis of (±)-elacestrant by employing two different coupling strategies: reductive amination of an aldehyde and nucleophilic substitution of a bromo compound with the core skeleton.

A series of novel substituted biimidazo[1,5-a]pyridine derivatives are synthesized via a robust three-step, bidirectional approach. The strategy involves an initial Negishi homocoupling of bromopicolinonitrile, followed by the formation of diketones with aryl Grignard reagents, and concludes with a double cyclization using substituted arylamines to afford a library of biimidazo[1,5-a]pyridines. Selected dimers are structurally characterized by single-crystal X-ray diffraction. In addition, the impact of substitution patterns and connectivity within the biimidazo[1,5-a]pyridine framework on their photoluminescent properties is systematically investigated. The key substitution position on imidazo[1,5-a]pyridine core for tuning optical properties is identified. Furthermore, density functional theory (DFT) calculations are conducted to complement the experimental findings, offering a deeper understanding of the electronic structure, planarity, highest occupied molecular orbital and lowest unoccupied molecular orbital properties that influence their performance as organic light-emitting materials for optoelectronic applications.

A stereoselective synthesis of protected macrocyclic lactone core structure of 13E-disciformycin B was accomplished in a convergent fashion employing commercially available (4S,5S)-2,2-dimethyl-1,3-dioxolane-4,5-dicarboxylate, tiglic aldehyde and (R)-Roche ester. Key transformations include an Aldol reaction, CBS reduction, Takai olefination, Julia olefination, Nozaki–Hiyama–Kishi (NHK) reaction, and Yamaguchi esterification reaction.

As a part of the ongoing COVID Moonshot project, an expedient approach to 1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylates is described. The method is based on a one-pot tandem Michael amination–lactamization sequence starting from 2-(3-alkoxymethoxy-3-oxoprop-1-en-2-yl)benzoic acids and primary amines. The scope of the N-nucleophiles included various aliphatic, aromatic, and heteroaromatic primary amines. The reaction tolerated and was compatible with ether, ester, amide, alcohol, carbamate, free alcohol, azole, or azine moieties. The developed protocol allowed for the preparation of target tetrahydroisoquinoline derivatives in 40%–75% yield on up to 109 g scale (later extended up to 0.86 kg). A mechanistic scheme involving a ring-chain tautomerism for the electrophilic component of the reaction is proposed. The method was used in the synthesis of DNDI-6510, a SARS-CoV-2 main protease inhibitor that showed promising results obtained in preclinical studies.

An unprecedented deprotonative functionalization of difluoromethoxylated compounds is described herein using a lithiated base under in situ trapping conditions. Aryl α,α-difluoroalkyl ethers could be obtained in a two-step process via difluoro(trimethylsilyl)methylated compounds without any intermediate purification. These new silylated scaffolds act as intermediates to mask the highly unstable difluorinated carbanion and to limit the formation of fluorocarbenes. Desilylative trapping with various electrophiles using a fluoride source gave rise to a library of new α,α-difluorinated ethers, which could be of particular interest in various fields such as life sciences or materials chemistry.