Journal of Organic Chemistry最新文献

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.

Aryl iodides are privileged intermediates in organic synthesis, underpinning cross-coupling chemistry, late-stage functionalization, and radiolabeling in medicinal chemistry. However, regioselective arene iodination remains a challenge, as traditional electrophilic iodination methods often require harsh conditions, exhibit poor selectivity, or suffer from limited functional group tolerance and substrate scope. We report a rapid and regioselective arene iodination enabled by Lewis acid activation of N-iodosaccharin. Iron(III) chloride and silver(I) triflimide were found to catalyze the efficient iodination of a broad range of electron-rich arenes at room temperature. The method displayed broad functional group tolerance and was applicable to complex substrates, including natural products and pharmaceuticals. Furthermore, the iodination was found to be compatible with cross-coupling reactions, allowing one-pot halogenation and arylation sequences for direct access to biaryl compounds.

A visible-light-driven cross-dehydrogenative coupling of azauracils with aldehydes is described by using dual acridinium photoredox and pyridine N-oxide hydrogen atom transfer catalysis. This oxidant-free method generates acyl radicals under mild conditions, tolerates diverse functional groups, proceeds under air, and is scalable to gram quantities. Mechanistic studies support the selective oxidation of pyridine N-oxide by the photoexcited catalyst, enabling aldehyde activation. This operationally simple protocol provides a sustainable platform for the late-stage functionalization of nitrogen-rich heterocycles.

Reaction of β-halo-β-(trifluoromethyl)styrenes with arylboronic acids can be directed in a different way depending on strength of the applied base and order of the reactant mixing. The standard Suzuki cross-coupling (Pd(OAc)₂/SPhos or Pd(PPh₃)₄) using K₃PO₄ or Na₂CO₃ as the bases afforded regio- and stereoselectively CF₃-containing 1,2-diarylethenes (CF₃-stilbenes) in up to 98% yield. However, pretreatment of these β-halo-β-(trifluoromethyl)styrenes with t-BuOK resulted in formation in situ of the corresponding CF₃-acetylenes. Subsequent Pd-catalyzed syn-addition of arylboronic acids can be performed as one-pot protocol to open access to CF₃-containing 1,1-diarylethenes having cis-arranged CF₃ group and aryl moiety of starting styrene. These alkenes were isolated in up to 96% yield. Both types of alkenes can be efficiently reduced into the corresponding CF₃-substituted ethanes using ammonium formate-Pd/C system.

N-H imines are synthetically versatile but sensitive intermediates in organic synthesis. This work introduces a cascade synthesis of basic amines through N-H imine intermediates, featuring an efficient aza-Norrish Type II fragmentation, followed by photoalkylation. Our method selectively converts bench-stable phenacylamines to α-quaternary primary amines in one pot using mild and metal-free UV photocatalysis. Our work constitutes a rare use of amine photofragmentation in organic synthesis.

Oxygen atom transfer (OAT) is a useful reaction in chemical synthesis, but because of the low reactivity of O₂ with organic substrates, harsh oxidants are often required. In contrast, metalloenzymes such as Cytochrome P450 catalyze a wide range of OAT reactions under mild conditions with O₂ as the source of the O atoms. In this work, we use a synthetic manganese porphyrin catalyst to mimic this reactivity. Our method enables electrochemical epoxidation of styrenes using O₂ through the generation of a Mn-superoxo intermediate. We report the reactivity of 12 styrene derivatives, with yields impacted by the position and electronic properties of the substituents. Spectroelectrochemical analyses indicate the generation of high-valent intermediates that enable epoxidation under these mild conditions.

An oxone-promoted radical annulation of 2-cyanoaryl acrylamides involving carbon–carbon double bond cleavage has been developed for the construction of 3-hydroxyquinoline-2,4(1H,3H)-diones. Such transformation exhibits good functional group tolerance and scalability. The reaction proceeds through an initial radical cyclization to form a 4-aminoquinolinone intermediate followed by hydroxylation to afford the final product.

Red algae of the genus Laurencia are prolific sources of halogenated C₁₅-acetogenins, many of which contain a tetrahydrofuran (THF) ring and a bromoallene terminus. Among them, Itomanallene B-type metabolites have presented a stereochemical paradox, as Laurencia intricata and Laurencia nangii yield epimeric structures despite sharing the same planar connectivity. In this study, we demonstrate that the chemical shift of the diagnostic C-4 proton provides a rapid and reliable indicator of the relative orientation (α,α′-syn vs α,α′-anti) of the THF side chains. Comparative analysis of reported NMR data reveals that anti configurations exhibit systematically more deshielded C-4 proton resonances than their syn counterparts. Applying this “chemical-shift litmus test” shows that Itomanallene B 1 from L. intricata possesses an α,α′-anti arrangement, whereas the metabolite previously reported as Itomanallene B 3 from L. nangii is instead the α,α′-syn epimer, 4-epi-Itomanallene B. This reassignment was unambiguously confirmed through the total asymmetric synthesis of the (aS,4S,6R,7R) stereoisomer of (+)-Itomanallene B, whose NMR data matched those of the natural product. The simplicity and diagnostic power of the C-4 proton chemical-shift approach provide an efficient tool for the stereochemical assignment of THF-containing C₁₅-acetogenins, addressing a recurrent source of structural misinterpretation within the Laurencia genus.