Organic & Biomolecular Chemistry最新文献

O-Benzoylhydroxylamines have been widely used as important amination reagents in C–N bond construction reactions; however, these reactions have exclusively focused on utilizing the amino group, with the benzoyloxy moiety often discarded as waste. Herein, we achieved the incorporation of both the NH₂ and benzoyloxy fragments of O-benzoylhydroxylamines into indole scaffolds via dearomatization of 4-alkyl-2-alkynylanilines and subsequent treatment with single-electron transfer (SET) reagents. The resulting 4-amino-7-oxyindoles allow for further selective structural modifications at the C-4 and C-7 positions as needed, facilitating drug screening investigations.

A mild, metal-free, and solvent-controlled reductive dechlorination method has been developed for synthesizing 3-chloro-2-oxindoles, and 2-oxindoles from 3,3-dichlorooxindoles. In this process, Rongalite serves as a mild reducing agent, achieving monodechlorination in polar protic, and complete dehalogenation in polar aprotic solvents, leading to the formation of 3-chloro-2-oxindoles, and oxindoles, respectively. This methodology features several advantages, including the use of inexpensive reagents, mild reaction conditions, simple operational procedures, high yields, and short reaction times.

The application of photocatalysis in organic synthesis has become essential because it enables mild, eco-friendly, and effective transformations to access essential molecular scaffolds. A sustainable and effective technique for generating spirocyclic compounds using photocatalysts is carried out via visible light-induced photochemical methods. This method enables the formation of intricate spirocyclic structures using easily accessible starting materials under moderate, eco-friendly conditions. Several visible light mediated spirocyclization reactions proceed via radical intermediates through a variety of processes, such as hydrogen atom transfer and single-electron transfer. The current developments in photocatalysed synthesis of spirocyclic compounds have been highlighted.

An iron-catalyzed protocol has been developed for the synthesis of unsymmetrical ureas via a cascade of oxidative C–N bond cleavage of tertiary amines and hydroamination of isocyanates. This strategy employs inexpensive FeCl₃ as the catalyst and aqueous TBHP as a benign oxidant in acetonitrile, enabling tertiary anilines to react with various isocyanates at room temperature. The protocol features a broad substrate scope and excellent functional group tolerance, while being operationally simple and scalable. It thus offers a practical and sustainable alternative for the synthesis of ureas.

Terpene synthases/cyclases catalyze the formation of complex polycyclic natural products via mechanisms proceeding through carbocation intermediates. Their active sites are generally lined with aliphatic and aromatic residues that prevent untoward termination of the reaction via carbocation deprotonation or addition of water, enabling use of the relevant catalytic base, whose positioning is then crucial to product outcome. This has been emphasized by studies with the ent-copalyl pyrophosphate synthase from Arabidopsis thaliana (AtCPS), representative of plant class II diterpene cyclases more generally, as displacement of its (conserved) catalytic base leads to such alternative product outcomes. Here we characterize the mechanistic basis for the profound effects of these disruptions in AtCPS using the TerDockin computational approach, combining quantum chemical electronic structure calculations and docking of the relevant carbocation intermediates, to provide insight into the underlying enzymatic structure–function relationships. Our predictions help identify important bases in the wild type and mutant systems of AtCPS, which include trapped water and the conjugate base of the catalytic acid that initiates terpene cyclization.

This study presents a BF₃·Et₂O catalyzed intramolecular cyclization reaction of ynones, enabling the efficient synthesis of spiro-heterocyclic compounds, such as spiro-γ-lactams and spiro-γ-lactones. This reaction enables the synthesis of diverse spirocyclic compounds under metal-free and mild conditions, exhibiting broad substrate compatibility and excellent yields.

A base-promoted [2 + 1] annulation reaction between iminoindoline-derived alkenes and 4-bromo-pyrazolones has been disclosed, affording a series of novel, pharmaceutically interesting spiro-cyclopropyl pyrazolones containing indolines in good to excellent yields with moderate to good diastereoselectivities. This protocol features broad functional group compatibility, simple operation, and mild reaction conditions.

A PyBroP/base-promoted three-component sequential decarboxylative nucleophilic addition protocol has been developed. Under the optimized conditions, a wide array of β-keto acids, isatylidene malononitriles and pyridine N-oxides couple efficiently to deliver the desired 3,3-disubstituted oxindole-fused pyridine derivatives in moderate to excellent yields. This method features good functional group tolerance, high positional selectivity, mild reaction conditions, and a one-pot procedure. The methodology can be scaled up to the gram scale, and the synthetic utility of the product was further validated. Control experiments have also been carried out to elucidate the plausible mechanistic pathway.

An efficient iodine-promoted four-component reaction has been developed for the synthesis of diverse polysubstituted pyrimidines from simple and readily available starting materials under metal-free conditions. The multicomponent strategy innovatively utilizes primary aliphatic amines as C–C–N synthons, aromatic aldehydes as C1 synthons and ammonium iodide as an environmentally benign nitrogen source, achieving α-C(sp³)–H and β-C(sp³)–H bond functionalization of primary aliphatic amines in one pot. This method offers a valuable alternative for synthesizing structurally diverse pyrimidines.

Electronic structure calculations were performed to assess how a β-boryl substituent modulates barriers for the classical Ei elimination of sulfoxides. Four main boron substituents were investigated: H, Me, F and OMe. Across the series, methanesulfenic-acid elimination exhibits reduced activation free energies and enthalpies as the boron functionality accepts electron density from the C_β–H bond, promoting a more asynchronous transition state with advanced C_β–H cleavage and O–H formation and correspondingly less S–C_α bond rupture relative to the benchmark ethyl methyl sulfoxide transition state. Nevertheless, β-boryl substrates of the 1B family access lower-energy minima that lead preferentially to boryl sulfenate elimination: the corresponding ΔG^‡ values are 9.5–15.5 kcal mol⁻¹ lower than for the competing proton-transfer (sulfenic-acid) pathway. Replacing methyl with vinyl or phenyl lowers ΔG^‡ by 1.9–4.9 kcal mol⁻¹ through enhanced stabilization of developing electron density at sulfur. A comparison of common boronic esters (catechol, pinacol, BMIDA) for both proton-transfer and boronic-ester-transfer pathways shows catechol (Bcat) gives the lowest barriers, whereas BMIDA is distinctive in that its methanesulfenic acid elimination resembles that of methyl ethyl sulfoxide, and boryl-sulfenate elimination is disfavoured owing to loss of intramolecular N → B coordination. Collectively, β-boryl substitution lowers Ei barriers via electron-acceptor stabilization and biases reaction manifolds toward boryl sulfenate elimination, with the extent governed by conjugation patterns and ester identity.