European Journal of Organic Chemistry最新文献

Herein, we report a photoinduced thiol–ene reaction for the synthesis of S-linked glycoconjugates derived from levoglucosenone and related renewable glycosyl scaffolds (cyrene, levoglucosenone, and aminocyrene). They were converted into the corresponding thiol derivatives through novel synthetic routes inspired by standard sugar chemistry. Thus, the resulting thiols were efficiently engaged in photocatalyzed hydrothiolation reactions using the TADF (thermally activated delayed fluorescence) compound 4CzIPN under mild visible-light irradiation, affording a library of S-linked glycomimetic products in high to quantitative yields with the allyl alcohol, tetraethyl ethene-1,1-diylbis(phosphonate), and Fmoc-protected allyl glycine derivative as acceptors. The protocol was further translated to aqueous conditions by employing a water-soluble 4CzIPN analog, enabling the direct functionalization of deprotected thiol derivatives with acrylamide in water. Finally, the methodology was successfully extended to conventional gluco-, galacto-, and manno thiosugar analogs, demonstrating broad applicability, excellent functional group tolerance, and compatibility with both protected and unprotected carbohydrate substrates.

A greener process for the oxidation of hydrocarbons containing primary, secondary, and tertiary benzylic carbon atoms, as well as aliphatic alcohols (e.g., cyclohexanol, menthol, and 4-heptanol) with molecular oxygen in supercritical carbon dioxide (scCO₂) medium under the visible-light irradiation in the presence of 2-fluoroanthraquinone (2-FAQ) as a photocatalyst (1 mol%) has been developed. The photooxidation reactions have been found to be accelerated by the addition of small amounts (1 equiv.) of water to the system. Plausible pathways for the promotion of the oxidation process have been identified: The most prominent is the cleavage of H─O bonds in the added water molecules under the action of the photocatalyst that results in extra reactive oxygen species generation. Also, a radical-chain mechanism for the photocatalytic process has been proposed. It is the first time that experimental data on the photophysical properties of 2-FAQ, including the redox potential of this promising photocatalyst in the photoexcited state, have been obtained.

In this work, we have investigated the visible-light-mediated thiol–ene coupling of N-acetyl-L-cysteine methyl ester with structurally distinct alkene-functionalized fluorophores using metal-free organic photocatalysts under mild conditions. The fluorophore set comprised naphthalene, naphthalimide, and aromatic diimide derivatives featuring different alkene environments and linker architectures. The transformations were promoted under mild and metal-free conditions using five organic photocatalysts belonging to three distinct structural families, namely acridinium salts, BOPHY derivatives, and xanthene dyes. The methodology proved to be compatible with structurally diverse fluorophore architectures and enabled the efficient preparation of both mono- and bis-functionalized cysteine conjugates. Reaction efficiency was influenced by fluorophore structure and photocatalyst identity, with yields reaching up to 95% for styrenyl naphthalimide derivatives. Sequential thiol–ene additions were successfully achieved for divinyl fluorophores, providing access to doubly functionalized products under the same reaction conditions. Photophysical studies demonstrated that cysteine incorporation generally preserves the absorption and emission characteristics of the parent fluorophores and, in several cases, leads to enhanced fluorescence quantum yields. These results establish visible-light-mediated thiol–ene coupling as a straightforward and versatile approach for the preparation of fluorescent cysteine building blocks from structurally diverse fluorophore scaffolds.

As modern weaponry and equipment evolve, there is an increasing demand for more powerful, less sensitive, and environmentally benign energetic materials. Fused heterocycle-based energetic materials, large conjugated systems composed of two or more rings that share adjacent atoms, exhibit superior thermal stability and higher density than their monocyclic and bridged analogs. Meanwhile, similar to cage heterocyclic rings, the fused structures generally possess higher heats of formation and elevated ring-strain energies, which enhance detonation performance. In addition, the fused backbones offer versatile modification sites, enabling researchers to balance energy and stability by introducing different functional groups. This review summarizes the research progress on 97 energetic fused heterocyclic compounds from the Web of Science (WOS) and Scopus databases since 2015 and presents their molecular design strategies, synthesis methods, and detonation properties. Furthermore, the major challenges are associated with the design of complex fused-ring frameworks and the large-scale preparation. This review highlights the insightful future research directions, particularly the development of universal synthesis strategies and the exploration of AI-driven automated design.

Direct Heck–Matsuda arylation of lapachol provides rapid access to structurally diverse naphthoquinones under homogeneous and heterogeneous palladium catalysis. The methodology features broad substrate scope, gram-scale applicability, and unambiguous structural assignment by single-crystal X-ray diffraction, providing an efficient platform for the diversification of quinones.

A base-promoted aza-Michael/S_N2′ and Michael-Nucleophilic addition sequential reaction enables efficient preparations of aza-bicyclic maleimides and tricyclic spiro-oxindoles in generally good yields (up to 99% yield) with excellent diastereoselectivities (up to 20:1 dr) from α-aminomaleimides and electron-deficient olefins.

A novel continuous-flow synthesis for the antipsychotic aripiprazole has been developed via a two-step, halogen-free route. The first step features the underutilized N-hydroxybutylation reaction employing in situ-generated THF hydroperoxide under reductive conditions. The continuous-flow setup ensures rapid and safe transformation through a telescoped sequence, incorporating on-demand generation and immediate quenching of the remaining hazardous reagent without isolation. This strategy was also applicable to the synthesis of other pharmaceutically relevant intermediates. The first step was integrated with a continuous-flow Mitsunobu reaction employing the Tsunoda reagent to give aripiprazole with high productivity. Overall, the developed process offers an environmentally benign alternative to conventional methods, achieving superior atom economy and reaction mass efficiency while eliminating the need for halogenated alkylating agents typically used in high excess.

Extensive research has been dedicated to developing sustainable and practical methodologies for installing fluoroalkyl groups into organic molecules, as such structural modifications can effectively tune the physicochemical and pharmacological properties of drug candidates. Despite significant advances, most established fluoroalkylation protocols still suffer from inherent drawbacks: conventional fluoroalkylating reagents are often expensive, thermally or chemically labile, and difficult to handle. Furthermore, their practical implementation usually requires stoichiometric redox chemicals to facilitate the generation of operative fluoroalkylating intermediates, compromising functional group tolerance and atom economy and ultimately restricting applicability in large-scale synthesis. This review summarizes recent advances in fluoroalkylations using widely available fluoroalkyl carboxylic acids as direct fluoroalkyl radical precursors, highlighting the unique merits, synthetic scope, and future potential of this emerging strategy.