A catalyst-free visible-light-induced dichlorination of alkenes has been developed using an N-chloro(fluorenone imine) reagent. The reaction proceeds through direct photoexcitation of the reagent under blue-light irradiation and enables vicinal dichlorination of aliphatic alkenes under mild conditions. Unprotected hydroxy and amino groups were tolerated, and comparable reactivity was observed under air. EPR analysis supported photoinduced N-Cl bond homolysis and was consistent with iminyl radical formation.
Abstract Isatogens are a unique class of heterocyclic compounds with electrophilic character provided by carbon–heteroatom multiple bonds. Historically, isatogens have been used as dyes and bioactive molecules, and their recent applications have focused mainly on regio- and stereoselective transformations using a C=N bond. Because we realized that the rapid synthesis of multisubstituted indolines with fused-ring systems could be a key methodology in our synthetic studies on complex alkaloids, we aimed to reveal new synthetic utility and focused on isatogens as suitable precursors for highly functionalized indolines. In this account, cyanation and [3+2] cycloaddition for the construction of tetrasubstituted carbons, as well as their application to alkaloid synthesis, are described.
Abstract In contrast to classical central, axial, planar, and helical chirality, inherent chirality represents a distinct form of molecular chirality. The catalytic asymmetric synthesis of novel inherently chiral macrocycles bearing catalytically active functional groups remains a frontier at the interface of asymmetric synthesis and supramolecular catalysis. Herein, we report a Pd/PC-Phos-catalyzed highly enantioselective macrocyclization that enables the de novo construction of DMAP-based inherently chiral macrocycles, affording up to 74% yield and 90% ee. This study lays the groundwork for the construction and application of functionalized inherently chiral molecules.
Abstract The recognition behavior of tetracationic cyclophanes is strongly influenced by the geometric match between the host cavity and aromatic guests. Herein, we compare two 3,3′-bipyridinium-based tetracationic cyclophanes, BPy-Box4+ and NBox4+, toward a series of naphthalene derivatives. 1H NMR titration experiments reveal cavity-dependent binding affinities and different recognition preferences. BPy-Box4+ binds naphthalene and hydroxylated naphthalene derivatives with comparable affinities in CD₃CN, whereas NBox4+ shows weak binding toward naphthalene but stronger association with selected hydroxylated guests. Chain-extended derivatives display lower affinities, suggesting that increased flexibility and steric bulk do not necessarily improve host–guest complexation. Computational analyses further support different preferred binding geometries in the two macrocyclic cavities. These results highlight cavity size and shape complementarity as key parameters for tuning the recognition behavior of tetracationic cyclophanes.
Abstract Herein, we report the selective transformation of N‑(4H‑1,2,4‑triazol‑4‑yl)imines into substituted benzonitriles. These imines are readily accessible from aldehydes. The method provides a rapid and mild procedure that utilizes a previously undescribed nitrogen source. This transformation offers excellent selectivity and facile product isolation. A series of aromatic nitriles bearing various functional groups were obtained in high yields (up to 98%).
Abstract For two-dimensional nanomaterials based on large π-conjugated ligands, the intrinsic tendency toward strong π–π interactions often drives isotropic stacking, which thermodynamically favors the formation of three-dimensional bulk architectures rather than extended two-dimensional sheets. Therefore, developing organic ligands with large π conjugation still presents significant challenges. Here, we design the perylene diimide (PDI) ligand by introducing bulky alkyl chains and vertically arranged terpyridine units, effectively suppressing excessive π–π stacking while promoting plane-coordination-directed growth. A two-dimensional PDI-based coordination polymer nanosheet (NS) is constructed at the liquid–liquid interface via steric hindrance modulation. The resulting ultrathin NSs could be used as photocatalysts for photocatalytic oxidation of benzylamine and thioanisole with high conversion rates and selectivity under mild conditions.
Abstract Herein, we report a modular and efficient synthesis of N-aryl-1,3,4-oxadiazol-2(3H)-one pharmacophores via Chan–Lam coupling of oxadiazolones with (hetero)arylboronic acids. This novel protocol employs readily accessible starting materials under mild, operationally simple conditions, along with wide substrate scope, rendering it a practical and versatile approach for the construction of diverse pharmaceutically relevant N-aryl-1,3,4-oxadiazol-2(3H)-one derivatives.
Bicyclo[1.1.0]butanes (BCBs) are versatile strain-release building blocks, yet their oxygenative transformations remain underdeveloped due to the instability of oxene intermediates. To address this challenge, we recently reported the use of pyridine N-oxide-derived triplet diradicals as stabilized oxene surrogates for BCB oxygenation. This Synpacts article highlights that work, tracing the conceptual foundations in pyridine N-oxide photochemistry and the reaction-design logic of the programmed ring-opening/reclosing sequence that underpins the transformation. The strategy provides efficient access to 5-oxa-2-oxo-bicyclo[2.1.1]hexanes (5-oxa-2-oxo-BCHexs) and related oxygenated scaffolds. Notably, the 5-oxa-2-oxo-BCHex motif reproduces the exit vectors of meta-substituted benzenes, highlighting its potential as a three-dimensional bioisostere in medicinal chemistry.
A dual catalytic approach enables the preparation of complex organic molecules from aryl carbonyl compounds in the presence of an organocatalyst and a photocatalyst under mild conditions. Dual catalytic methods offer late-stage functionalization of drugs and bioactive compounds. This review covers recent advances (2020-2025) in the development of dual catalysis and their synthetic applications. Furthermore, the described dual catalytic methods address current synthetic challenges and future opportunities for developing more efficient catalytic systems and straightforward carbonyl functional group transformations under green, cost-effective photochemical conditions that tolerate a wide range of functional groups and commercially available aromatic carbonyl compounds, as well as inexpensive, nontoxic reagents. This review paper focuses on functional group transformations and their related synthetic applications.
Herein, a metal-free and environmentally benign visible-light-induced photocatalytic system for the oxidation of benzyl alcohols was developed, employing 4-bromoacetophenone as the photocatalyst under an O2 atmosphere at room temperature, affording the desired products in up to 88% yield. This strategy demonstrates broad substrate compatibility across a range of substituted benzyl alcohols. The products were obtained with high purity, and the reaction exhibited excellent robustness, good reproducibility, and demonstrated feasibility for scale-up. Combined with systematic mechanistic investigations, the reaction pathway has been further elucidated, providing a new approach for visible-light-driven selective oxidation. This operationally simple and sustainable protocol offers a practical alternative for alcohol oxidation, which will benefit the organic synthesis and green chemistry community.
Abstract An efficient and eco-friendly method for synthesizing a novel class of perylene- and pyrene-based frameworks was developed using Morita–Baylis–Hillman (MBH) adducts of isatin derivatives with anthracene, achieving good yields under metal-free conditions mediated by K-10 clay. The resulting spiroperylene and spiro-pyrene derivatives exhibited orange-red fluorescence, demonstrating a significant influence of the MBH adduct on the fluorescence behavior of anthracene. Specifically, with 1 equiv of the MBH adduct, anthracene displays green fluorescence, while with 2 or 3 equiv, the emission shifts to orange-red, indicating a notable change in its photophysical properties. This transformation provides a sustainable approach to accessing fluorescent organic materials, which could be valuable for applications in sensing, optoelectronics, and material science.
Abstract A novel, convenient, and one-pot, three-component method for the synthesis of 1,2,4-triazoles with calcium carbide as an acetylene has been developed in a catalytic condition. The present synthesis includes the reaction of alkyl halides with sodium azide followed by the reaction with calcium carbide under commercially available CuSO4 catalyst. The impact of solvents, temperature, and catalysts are included in this report. The presented method has a broad substrate scope, and various corresponding 1,2,3-triazoles have been obtained in good-to-excellent yields.
The Norrish-Yang photocyclization is a well-established method to access cyclobutanols from simple ketone starting materials. However, access to three-membered ring systems has remained limited due to the strong kinetic preference for 1,5- over 1,4-hydrogen atom transfer. To address this long-standing challenge, we recently developed a novel photocyclization strategy that enables the synthesis of cyclopropanols from beta-boryl aryl ketones, in yields ranging from 25% to 96%. This approach relies on the selective population of the pi,pi* triplet excited state over the n,pi* triplet state, enabling preferential 1,4-boryl group transfer over 1,5-HAT. The resulting protocol proceeds under mild irradiative conditions, exhibits broad functional group tolerance, and provides efficient access to a diverse set of cyclopropanol scaffolds. Due to the readily accessible starting materials, along with the simple reaction conditions and set-up, we anticipate that this method will facilitate access to 1-aryl cyclopropanols.
Carbohydrates not only serve as energy sources for organisms but also perform numerous critical physiological functions. However, the inherent instability of the O -glycosidic bonds restricts their application as therapeutic agents, and glycomimetics (including C -glycosides, branched-chain sugars, and carbasugars) have emerged as highly promising carbohydrate surrogates. We have developed a photoinduced hydrogen atom transfer (Photo-HAT)/nickel dual-catalytic system, which enables direct and stereoselective C(sp(3))-H bond functionalization of carbohydrates, thereby providing a novel technology for the efficient synthesis of diverse rare sugars such as C -glycosides, branched-chain sugars, and carbasugars.
Phthalides are prevalent structural motifs in bioactive natural products, yet their efficient synthesis remains challenging. Herein, we report an intramolecular Alder-Rickert cascade strategy for the rapid assembly of the phthalide framework, enabling the simultaneous construction of both the gamma-lactone and benzene rings. This approach was applied to the synthesis of the proposed structure of kerriin A in 7 steps from commercially available starting materials, with an overall yield of 11%. Comparison of the spectroscopic data of the synthetic material with those reported for the natural product revealed clear discrepancies, suggesting that the reported structure of kerriin A may require revision and is likely a positional isomer.
Herein, we report a new methodology for the synthesis of alkyl enol ethers via the coupling of alkenyl bromides and alkoxy radicals under blue LED irradiation. N,N-Dimethyl formamide di-tert-butyl acetal serves as a precursor to tert-butoxy alkoxy radicals. The generated tert-butoxy alkoxy radicals function as hydrogen atom transfer (HAT) agents, enabling the formation of structurally diverse alkoxy radicals from a wide range of alcohols. Utilizing these alkoxy radicals in combination with alkenyl bromides allows the efficient synthesis of a variety of enol ethers in up to 80% yield, and the reaction exhibits good scalability. This strategy provides a mild and versatile platform for enol ether synthesis and is expected to facilitate broader application of alkoxy radical chemistry in organic synthesis.
The catalytic, asymmetric intramolecular iodoetherification of ortho-allylphenols was achieved using a multinuclear zinc bis(aminoimino)binaphthoxide complex, generating dihydrobenzofuran compounds in up to 99% yields with 85% ee. Azidation of the chiral compound 2-iodomethyldihydrobenzofuran and a subsequent click reaction with phenylacetylene gave the corresponding triazolesubstituted dihydrobenzofuran while maintaining the original chirality.
Abstract Heterocyclic compounds are of significant importance in the fields of organic synthesis and medicinal chemistry. Current synthetic methods for these molecules often rely on specific building blocks or transition-metal catalysis, which impose certain limitations in terms of methodology. Consequently, the development of metal-free synthetic methodologies for heterocycles is of great importance. In this study, readily available and inexpensive additives, TsOH·H₂O and CH₃COOH, were employed as the mediators. By modulating the solvent system, isocoumarin and isoquinoline derivatives were efficiently synthesized in CH₃CN and DMF, respectively. Notably, this method enables a rapid and efficient synthesis of the natural product Thunberginol A under metal-free conditions. This strategy offers a practical and efficient approach for constructing relevant drug-like core skeletons.
