Journal of Organic Chemistry最新文献

A highly efficient and versatile strategy has been developed for the synthesis of 3-brominated thioflavonoids and benzothiophenes from readily available alkynes by using tetrabutylammonium bromide (TBAB) as the bromine source. This transformation proceeds smoothly via photocatalyzed, regioselective bromination/cyclization under metal- and additive-free conditions, with excellent functional group tolerance. This protocol enables the efficient construction of biologically relevant brominated heterocycles in up to 99% yield for 37 examples, thus offering a valuable protocol for directly introducing bromine into diverse thioflavonoids and benzothiophenes.

An efficient one-pot protocol is devised to access a wide range of sulfenamide derivatives through the copper-catalyzed coupling of sulfonyl azides with thioamides. The reaction proceeds via a copper–nitrenoid intermediate derived from sulfonyl azides, enabling chemo- and regioselective construction of the S–N bond through the extrusion of nitrogen as the sole byproduct. Notably, the protocol exhibits broad functional group tolerance and scalability. Scale-up reactions and mechanistic studies further underscore the operational simplicity, mild nature, and synthetic utility of this transformation.

An efficient photocatalytic protocol combining heterogeneous semiconductors as photocatalysts and Ph₃N as a redox reagent was disclosed. Under this protocol, phenanthridine-6-carboxamides were formed in up to 93% yield via a multicomponent radical cascade annulation. Good substituent tolerance and gram-scale reaction showed the potential in fine chemical modification and pharmaceutical synthesis.

Achieving high enantioselectivity in reactions involving substrates bearing remotely positioned substituents with nearly identical steric and electronic properties represents an outstanding challenge in asymmetric catalysis. Herein, we describe a local stereocontrol strategy mediated by a confined chiral Brønsted acid catalyst that exerts precise stereodifferentiation at the prochiral epoxide center, resulting in the formal stereodifferentiation of minimally distinct remote substituents, such as methyl vs ethyl or C₆D₅ vs C₆H₅, located up to nine bonds away from the reactive center. Computational studies reveal that localized stereorecognition at the reaction site translates into significant energy differences between diastereomeric transition states, rationalizing the high stereoselectivity. Beyond introducing a novel paradigm for achieving enantioselectivity through formal remote stereodifferentiation, this method also establishes a catalytic asymmetric route to donor–acceptor type chiral spirofluorenes, which exhibit promising properties as solvatochromic probes, live-cell imaging agents, and circularly polarized luminescence emitters.

Imidazole-4(2H)-ones are extensively studied in synthetic chemistry communities as important motifs and exhibit intriguing biological activities that are crucial for lead compound discovery. Thus, the development of efficient and green synthetic strategies for the preparation of imidazole-4(2H)-ones has attracted significant attention. Herein, a catalyst-free cascade annulation reaction of isatin-derived N-unprotected ketimines with α-ketoamides is reported, furnishing a variety of spiro-imidazole-4(2H)-one oxindole derivatives in good to excellent yields. Furthermore, gram-scale preparation and synthetic transformations demonstrate the practicality and utility of the current cascade reaction.

Understanding and predicting catalyst performance from structural and electronic information remains a central challenge in organocatalysis. Here, we present a data-integrated framework that quantitatively combines experimental, computational, and machine learning (ML) approaches to elucidate the structure–activity relationships of halogen-bond (XB) donor catalysts based on perfluoroiodoarene cores. Single-crystal X-ray diffraction and chloride-binding analyses revealed that linker-containing two-point donors exhibit significantly stronger binding and higher catalytic activity than one-point donors. Through density functional theory calculations and an ML regression analysis integrating crystallographic and electronic descriptors, the Gibbs free energy change (ΔG) and binding constant (K) were identified as primary determinants of activity. Meanwhile, a Shapley additive explanation analysis highlighted the σ/π-hole potentials and nucleophilicity (N value) as additional electronic factors. This integrated experimental–computational–ML approach enables the quantitative extraction of key electronic factors governing XB donor catalysis and provides a physically interpretable framework for extending noncovalent-interaction-driven organocatalysis beyond XB formation, encompassing hydrogen- and chalcogen-bond donor systems.

Here, we demonstrated a metal-free, Brønsted acid-catalyzed, regioselective nondirected C–H activation reaction that efficiently achieves ortho-functionalization of p-anisidines via quinone imine ketals. Besides streamlining the synthesis of ortho-azidated anilines, our method is scalable and exhibits a high tolerance to various functional groups. Control experiments and comprehensive 2D NMR analysis confirmed the ortho-selectivity. The protocol was also adapted to synthesize difficult diaminated arenes and successfully used to produce marketed proton-pump inhibitors, Ufiprazole and Omeprazole.

A concise and efficient second-generation synthesis of 2-(2-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)benzoic acid (TBBA) has been developed. The synthesis affording enantiomerically pure TBBA atropisomers was significantly streamlined through optical resolution by diastereomeric salt formation, enabling preparation on a 32 mmol scale. The applicability of TBBA as a chiral derivatizing agent in the solid-phase synthesis of amino acid derivatives was demonstrated, allowing determination of the absolute configuration and optical purity by ¹H and ¹⁹F NMR spectroscopy. Furthermore, ¹⁹F NMR analyses were successfully carried out on a low-field benchtop NMR spectrometer, including samples dissolved in nondeuterated solvents.

The incorporation of a nitrogen unit into target molecules by generating nitrene species has become a hot topic in modern organic synthesis. In this study, we report a Co(III)-catalyzed C5–H amination of thiochromones with anthranils as aminating surrogates. The significance of this coupling reaction was demonstrated via a broad range of substrates and complete site selectivity. Moreover, post-transformations of synthesized products are described.