Journal of Organic Chemistry最新文献

Oxidized photoproducts of pyridinium bisretinoid A2E, including the mono- and bishexahydrobenzofurans, which have been isolated from lipofuscin in the retinal pigment epithelium (RPE) cells of human eyes, have been synthesized in enantiopure form using as key step a Horner-Wadsworth-Emmons (HWE) condensation reaction of pyridinecarbaldehydes and enantiopure cyclohexene oxide pentadienylphosphonates. The synthesis of the trienylcyclohexene oxide branch on the shorter arm (S) of the pyridine ring was followed by a diastereoselective rearrangement to the hexahydrobenzofurandienyl substituent under acidic conditions. In contrast, the construction of the polyenic long arm (L) of the pyridine ring by HWE condensation evolved to the formation of diastereomeric hexahydrobenzofurantrienyl substituents in an unselective rearrangement. The alternative and more straightforward bidirectional HWE condensation of the cyclohexene oxide pentadienylphosphonates with 4-formylpyridine-2-butenal afforded a more complex mixture of products, from which the bishexahydrobenzofurans together with the 11-cis double bond isomer and a rearrangement product in S were also characterized. DFT studies on model systems provided a mechanistic rationale for these transformations. The pyridinium bisretinoid hexahydrobenzofurans underwent aggregation upon nanoprecipitation using methanol/water solvent mixtures, and (5′R,8′R)-L-trans-hexahydrobenzofuran-A2E (9a) was shown by TEM to form spherical aggregates.

An oxidative hetero coupling reaction between 2-oxindoles and phenols was developed using a guanidinium/hypoiodite catalytic system. This reaction enables the efficient construction of 3-aryl-2-oxindole scaffolds under mild conditions. Furthermore, oxidative heterocoupling employing a chiral guanidinium organocatalyst in combination with hypoiodite afforded enantio-enriched products with moderate enantioselectivity.

Nonactivated 1,3-enynes react with cyanamides under gold(I)-catalyzed conditions. This divergent interplay proceeds as [4 + 2]-bimolecular or [2 + 2 + 2]-trimolecular cycloadditions and affords 2-aminopyridines, 1-aminoisoquinolines, and 2,4-diaminopyrimidines. The impact of catalytic systems and electronic/steric parameters on reaction selectivity was studied, and these findings enable directing the cycloaddition along the desired pathway. As a result, a new highly selective modular approach to valuable 2-aminopyridines was proposed. The further synthetic potential of this methodology was demonstrated through postmodifications, including functionalizations of both the heterocyclic backbone and amino substituents.

Herein, we developed a visible light-induced hydrosulfonylation of terminal alkynes using sulfonyl chloride via a collision complex between solvent and substrate. Such a method features a broad substrate scope and demonstrates its effectiveness in the synthesis of biologically active molecules. This is the first report on the synthesis of vinyl sulfone-based compounds without any metal catalysts, extra oxidants, or additives and paves the way for an in-depth understanding of the lone pair−σ complex photochemistry between solvent and substrate.

DFT calculations have been used to investigate the conformational landscape of a library of 1,3-bis[oxo/thioxo-thiazolinyl] aromatic compounds with two stereogenic C_sp2-N_sp2 axes (63 compounds). The good correlation between the experimental and DFT-calculated rotational barriers for five of these compounds allowed the use of DFT as a predictive tool for the entire library. The library was generated by systematically varying the position and number of methyl substituents on the central aromatic ring and on the two oxo/thioxo-thiazoline rings. The predicted rotational barriers span from 3 to 58 kcal/mol at 298.15 K, placing these structures across all three categories defined by LaPlante’s classification of rotational stereoisomers. DFT calculations unveiled the preferred rotational pathways, highlighting the main factors influencing the energetic cost of the rotation: intramolecular donor–acceptor interactions, ring distortions, and the nature of the exocyclic heteroatom of the thiazoline rings. The structure–rotational barrier relationship obtained for these molecules with two C–N stereogenic axes represents reference values for the design of atropisomers with aryl-thiazoline scaffolds for various applications, such as chiral bioactive compounds. Also, ¹⁵N NMR data are reported for some of the synthesized compounds.

We present a method for the silver-catalyzed oxacyclization of 3-alkynylpyrroles to create the pyrano[3,4-b]pyrrolone scaffold. This method exhibits high regioselectivity, enabling position-specific functionalization of the pyrrole core without the need for N-protection. It is also compatible with a broad range of substrates. Using this strategy, we synthesized a small library of novel triarylated pyranopyrroles, thereby enabling the creation of substitution patterns that were previously challenging to achieve. This methodology, therefore, provides a versatile approach to heteroaromatic architectures that are potentially relevant in drug discovery and chemical biology.

The photocatalytic carbofunctionalization of N-sulfinylamines offers an efficient route to diverse sulfinamides, yet the direct use of inexpensive boronic acids as radical precursors has been limited due to their high oxidation potentials. To address this, we developed a Lewis base-assisted strategy that generates a sp³-hybridized tetracoordinated boronate complex in situ with a markedly lowered redox potential. This approach enables a practical and atom-economical photocatalytic synthesis of sulfinamides directly from N-sulfinylamines and commercially available boronic acids.