Beilstein Journal of Organic Chemistry最新文献

The batch processes of APIs/pharmaceutical synthesis are prone to suffer significant limitations, including longer process time, shortage of skilled manpower, laborious post-synthetic work-up, etc. To address the inherent limitations of batch processes, a novel approach was undertaken, resulting in the establishment and development of a visible light-assisted modular photo-flow reactor with a seamlessly integrated post-synthetic work-up procedure enabling the efficient synthesis of dihydropyranones from furfuryl alcohols. The reaction uses sun light as green energy source, and the novel photo-flow reactor platform developed with an integrated system enabling a downstream process in a time and labor-efficient manner which facilitates the Achmatowicz rearrangement, resulting in a fast (10 min) formation of the dihydropyranone products.

This review surveys the recent advances and challenges in predicting and optimizing reaction conditions using machine learning techniques. The paper emphasizes the importance of acquiring and processing large and diverse datasets of chemical reactions, and the use of both global and local models to guide the design of synthetic processes. Global models exploit the information from comprehensive databases to suggest general reaction conditions for new reactions, while local models fine-tune the specific parameters for a given reaction family to improve yield and selectivity. The paper also identifies the current limitations and opportunities in this field, such as the data quality and availability, and the integration of high-throughput experimentation. The paper demonstrates how the combination of chemical engineering, data science, and ML algorithms can enhance the efficiency and effectiveness of reaction conditions design, and enable novel discoveries in synthetic chemistry.

Herein, we present 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as an efficient solvent for synthesizing resorcin[n]arenes in the presence of catalytic amounts of HCl at ambient temperature and within minutes. Remarkably, resorcinols with electron-withdrawing groups and halogens, which are reported in the literature as the most challenging precursors in this cyclization, are tolerated. This method leads to a variety of 2-substituted resorcin[n]arenes in a single synthetic step with isolated yields up to 98%.

The direct nucleophilic addition of amides to unfunctionalized alkenes via photoredox catalysis represents a facile approach towards functionalized alkylamides. Unfortunately, the scarce nucleophilicity of amides and competitive side reactions limit the utility of this approach. Herein, we report an intramolecular photoredox cyclization of alkenes with β-lactams in the presence of an acridinium photocatalyst. The approach uses an intramolecular nucleophilic addition of the β-lactam nitrogen atom to the radical cation photogenerated in the linked alkene moiety, followed by hydrogen transfer from the hydrogen atom transfer (HAT) catalyst. This process was used to successfully prepare 2-alkylated clavam derivatives.

A change in mechanism was observed in the hypervalent iodine-mediated cyclization of N-alkenylamides when the carbon chain between the alkene and the amide increased from two to three atoms. In the latter case, cyclization at the amide nitrogen to form the pyrrolidine ring was favored over cyclization at the amide oxygen. A DFT study was undertaken to rationalize the change in mechanism of this cyclization process. In addition, reaction conditions were developed, and the scope of this cyclization studied.

In this work, we describe the synthesis of halogenated pyran analogues of ᴅ-talose using a halo-divergent strategy from known 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-ᴅ-mannopyranose. In solution and in the solid-state, all analogues adopt standard ⁴ C ₁-like conformations despite 1,3-diaxial repulsion between the F2 and the C4 halogen. Moreover, the solid-state conformational analysis of halogenated pyrans reveals deviation in the intra-annular torsion angles arising from repulsion between the axial fluorine at C2 and the axial halogen at C4, which increases with the size of the halogen at C4 (F < Cl < Br < I). Crystal packing arrangements of pyran inter-halides show hydrogen bond acceptor and nonbonding interactions for the halogen at C4. Finally, density functional theory (DFT) calculations corroborate the preference of talose analogues to adopt a ⁴ C ₁-like conformation and a natural bonding orbital (NBO) analysis demonstrates the effects of hyperconjugation from C-F antibonding orbitals.

Trifluoromethoxylated molecules and selenylated compounds find a wide range of interesting applications, but separately. In order to combine the potential of these two motifs and to propose a new class of compounds, we have developed an electrophilic phenylseleno trifluoromethoxylation of alkenes, which leads to β-selenylated trifluoromethoxylated compounds or, upon subsequent reduction, to the trifluoromethoxylated ones.

We describe herein a facile method to access 2,3-epoxyesters with fluorine-containing substituents at their 3-position starting from the corresponding enoates by utilization of the low-costed and easy-to-handle reagent, NaOCl·5H₂O. Because very little has been disclosed about the reactivity of such 2,3-epoxyesters, their epoxy ring opening by a variety of nucleophiles was carried out and we succeeded in clarifying these chemo- as well as regioselective processes proceeding via the S_N2 mechanism to mainly afford 2-substituted 3-hydroxyesters usually in a highly anti selective manner.

Nitration of O-methylisouronium sulfate under mixed acid conditions gives O-methyl-N-nitroisourea, a key intermediate of neonicotinoid insecticides with high application value. The reaction is a fast and highly exothermic process with a high mass transfer resistance, making its control difficult and risky. In this paper, a homogeneous continuous flow microreactor system was developed for the nitration of O-methylisouronium sulfate under high concentrations of mixed acids, with a homemade static mixer eliminating the mass transfer resistance. In addition, the kinetic modeling of this reaction was performed based on the theory of NO₂ ⁺ attack, with the activation energy and pre-exponential factor determined. Finally, based on the response surface generated by the kinetic model, the reaction was optimized with a conversion of 87.4% under a sulfuric acid mass fraction of 94%, initial reactant concentration of 0.5 mol/L, reaction temperature of 40 °C, molar ratio of reactants at 4.4:1, and a residence time of 12.36 minutes.

Diaryliodonium(III) salts have been established as powerful halogen-bond donors in recent years. Herein, a new structural motif for this compound class was developed: iodoloisoxazolium salts, bearing a cyclic five-membered iodolium core fused with an isoxazole ring. A derivative of this class was synthesized and investigated in the solid state by X-ray crystallography. Finally, the potential as halogen-bonding activator was benchmarked in solution in the gold-catalyzed cyclization of a propargyl amide.