Organic & Biomolecular Chemistry最新文献

A ruthenium-catalyzed one-pot sequential cascade has been developed for the synthesis of functionalized pyridazino[4,5-b]quinolin-1(2H)-ones. The sequence comprises Ru/Cu-catalyzed C(sp³)–H oxidation, cyclization with hydrazine hydrate, Chan–Lam N–H arylation, and Ru/Cu-mediated ortho-selective C(sp²)–H alkenylation in a single operation. Mechanistic studies highlight the crucial role of ruthenium in C–H activation and alkenylation. The N-aryl substitution of pyridazino[4,5-b]quinolin-1(2H)-one resulted in steric hindrance, which prevents free rotation around the C–N single bond (CN nature due to the amide, phenyl, and ortho bulky substituents), and hence showed inherent atropisomerism, as revealed by specific optical rotation (SOR) studies. Furthermore, the alkenylation at the o-position enhanced the restriction of free rotation and the atropisomeric products were obtained, as revealed by chiral HPLC analysis and SOR studies. However, further detailed chiral synthetic studies are required to understand the enantioselective versions, which are in progress in our laboratory and will be communicated separately. SC-XRD studies revealed that the crystallization of products occurs in centrosymmetric space groups. This efficient cascade offers a concise route to structurally diverse atropisomeric and functionalized pyridazinoquinolinones.

A diene-transmissive hetero-Diels–Alder strategy, grounded in previous experimental works and employing boronated dienophiles, is proposed for the synthesis of boron-bearing octahydroquinolines. To assess its feasibility, three representative reactions were investigated, and their thermodynamics were evaluated in toluene and acetonitrile at various temperatures using the ωB97X-D level of theory. The peri-, regio-, stereo-, and π-facial selectivities were predicted. The reaction mechanisms were elucidated through exploration of the reaction pathways and topological studies using the Electron Localization Function and Independent Gradient Model. The predictions are consistent with available experimental work and show that the reactions are feasible with low to moderate polarity. The results also demonstrate that the selectivity of the reactions can in some cases be tuned by judicious choice of reaction conditions to deliver specific products with high selectivity.

Herein, a nickel-catalyzed isocyanide insertion reaction with aromatic amines under open-air conditions is disclosed. A number of open-chain guanidines are successfully synthesized in moderate to good yields and their structures are confirmed by X-ray diffraction analysis. This reaction features mild reaction conditions, readily available starting materials and easy operation. Halogen atoms including F, Cl, Br and I are all compatible with the reaction. Mechanistic studies reveal that oxygen in the air might act as an oxidant.

A diastereoselective efficient synthesis of 5′H-spiro[indoline-3,2′-oxazol]-2-ones bearing a pharmacophore phthalimide fragment was developed. The approach is based on the thermal ring opening of spiro-aroyl-N-phthalimidoaziridine oxindoles, which are readily accessible via aminoaziridination of methylideneoxindoles. The formation of the final spiro compounds proceeds through the generation of azomethine ylides, followed by a selective 1,5-electrocyclization involving the aroyl carbonyl group and a formal 1,3-migration of the phthalimide substituent. The mechanism was confirmed by DFT calculations.

Correction for ‘Design, synthesis, biological evaluation and molecular docking studies of quinoline–anthranilic acid hybrids as potent anti-inflammatory drugs’ by Sidra Siddique et al., Org. Biomol. Chem., 2024, 22, 3708–3724, https://doi.org/10.1039/D4OB00040D.

Metal hydride hydrogen atom transfer (MHAT) has emerged as a powerful strategy for alkene hydrofunctionalization, offering high levels of chemo-, regio-, and stereocontrol. In recent years, this reaction has provided new retrosynthetic disconnections in the total synthesis of natural products. Its intrinsic Markovnikov selectivity, broad steric and functional group tolerance, and ability to enable polarity inversion make MHAT particularly well suited for tackling synthetic challenges in complex molecular architectures. This review highlights recent total syntheses that employ MHAT-induced reactions as the key steps, with particular emphasis on reaction optimization and the mechanistic basis of chemo- and stereoselectivity. The advantages and limitations of MHAT relative to traditional hydrofunctionalization approaches are also discussed. Together, these advances underscore the versatility and impact of MHAT as a central platform in natural product synthesis.

This work describes an efficient Pd-catalyzed synthesis of benzo[4,5]imidazo[1,2-a]indoles from readily available 1-(2-iodophenyl)-1H-indoles and di-t-butyldiaziridinone. A variety of benzo[4,5]imidazo[1,2-a]indoles can be obtained in up to 96% yield. The reaction likely proceeds via an intramolecular aryl C–H activation to form a pallada(II)cycle, which is subsequently bisaminated with di-t-butyldiaziridinone.

Correction for ‘C–H bond cyanation: electrochemical synthesis of phenylbenzimidoyl cyanide derivatives’ by Najoua Sbei et al., Org. Biomol. Chem., 2025, 23, 4917–4921, https://doi.org/10.1039/d5ob00522a.

A stereoselective route to access substituted pyrrolidine cores via Lewis acid catalyzed (3 + 2)-annulation of donor–acceptor cyclopropanes (DACs) and isoxazolines has been developed. Exclusive cis-2,5-stereoselectivity was governed by kinetically controlled conditions using Sn(OTf)₂ as the catalyst, while excellent trans-2,5-stereoselectivity was achieved by thermodynamically controlled conditions using Sc(OTf)₃ as the catalyst. For DACs bearing electron-poor substituents, Yb(NTf₂)₃ proved to be the most efficient catalyst due to its higher Lewis acidity compared to triflates. The isoxazoline (3 + 2)-annulation reaction was also extended to bicyclo[1.1.0]butanes (BCBs), providing easy access to the 2-azabicyclo[2.1.1]hexane core, which may be considered as a promising 3D-bioisosteric replacement for pyrrole and pyrrolidine motifs.

A chemoselective reduction of α-keto aldehydes using rongalite in water has been developed for the efficient synthesis of α-hydroxymethyl ketones. This transformation exploits the unique reactivity of rongalite to achieve a mild, metal- and hydride-free reduction that proceeds smoothly in the presence of various functional groups. The protocol employs inexpensive rongalite (ca. $0.03 per gram), operates in an aqueous medium under open-air conditions, and requires no inert atmosphere. The reaction is readily scalable to gram quantities and exhibits excellent chemoselectivity and broad substrate scope, tolerating electron-donating, electron-withdrawing, and halogen substituents, as well as hetero aromatics, delivering the desired products in high yields within short reaction times.