ACS Organic & Inorganic Au最新文献

Hydroxylamine (NH₂OH), an N-O containing moiety and a pivotal intermediate in the nitrogen biogeochemical cycle, typically functions under reducing conditions, in stark contrast to its isoelectronic O-O analogue, hydrogen peroxide (H₂O₂). Oxygen-substituted hydroxylamine derivatives, widely employed in organic synthesis, utilize electron-withdrawing substituents (R) to weaken the N-O bond, thereby enabling the generation of reactive "N-transfer" intermediates. Although these reagents are increasingly recognized for their dual roles as masked "amine" donors and potential "oxidants", direct experimental validation of their oxidative capacity has remained elusive. Herein, we report a detailed mechanistic investigation integrating kinetic, spectroscopic, electrochemical, and computational approaches to establish the dual functionality of O-acyl-substituted hydroxylamine derivatives in iron-catalyzed N-transfer processes. Using a series of O-benzoyloxy hydroxylamine-derived triflic acid salts bearing electronically varied substituents (Ox_Me, Ox_OMe, Ox_H, and Ox_NO2 ) along with the O-pivaloyl hydroxylamine derivative (PivONH₃OTf), (Ox_OPiv), a clear structure-function relationship was uncovered, where the modulation of the electron density on the oxygen substituent tunes the redox potential and thus the oxidizing strength of the O-acyl-substituted hydroxylamine-derived N-O reagents. Mechanistic probing using well-defined outer-sphere Fe-(II) redox probesferrocene (Fc) and decamethylferrocene (DMFc)demonstrates that O-acyl-substituted hydroxylamine derivatives promote Fe-(II) to Fe-(III) oxidation via the outer sphere electron-transfer process. However, while Fc undergoes oxidation to ferrocenium ion (Fc⁺) along with the formation of putative iron-nitrogen/N-inserted intermediates (detected by high-resolution mass spectrometry), the sterically hindered, methyl-substituted DMFc exhibits a pure outer sphere redox event to form decamethylferrocenium ion (DMFc⁺) without competing N-substitution reactivity on the cyclopentadienyl (Cp) backbone. Together, these results provide the first direct experimental evidence for the oxidative capability of O-acyl-substituted hydroxylamine derivatives via a reductive N-O bond cleavage. This study unveils a mechanistically distinct pathway for the advancement of catalytic amination reactions and guides the design of sustainable nitrogen-transfer methodologies.

Oxazolidinones are important heterocyclic compounds with several therapeutic properties, especially antimicrobial activity, as seen in linezolid. Unexpectedly, a 2-oxazolidinone structurally similar to linezolid was obtained, prompting optimization of the reaction methodology and quantum calculations to rationalize the experimental observation. The reaction proceeded efficiently in refluxing water, in which computational analysis identified a remarkable and unprecedented stable reaction intermediate, enabling possible anchimeric assistance. Water significantly accelerates the process by lowering energy barriers and facilitating epoxide ring-opening through hydrogen bonding catalysis, as supported by density functional theory calculations.

Nickel-catalyzed electrochemical cross-coupling has emerged as an important advancement in synthetic chemistry, combining the versatile catalytic properties of nickel with the sustainability and precision of electrochemical methods. This review captures the recent progress in this dynamic field, focusing on developments published from 2015 onward, and emphasizes the development of innovative catalytic systems and reaction conditions that enhance efficiency, selectivity, and environmental sustainability. Key advancements include novel nickel catalysts, expanded substrate scopes, and mechanistic insights that elucidate the synergistic benefits of electrochemical approaches. By exploring these recent developments, we highlight the transformative potential of nickel-catalyzed electrochemical cross-coupling in facilitating complex bond formation under mild conditions. This comprehensive overview provides a foundation for understanding the current state and future directions of this promising area, emphasizing its significance in advancing green and efficient synthetic methodologies.

β-Hydroxysulfides are valuable intermediates in pharmaceutical and synthetic chemistry. In this study, we present an efficient method for synthesizing β-hydroxysulfides via the radical pathway for sulfurization reaction of alkenes using Zn-(OAc)₂·2H₂O as an inexpensive and environmentally friendly catalyst, yielding products in good to excellent yields. Notably, vinylpyridine serves as an effective substrate, leading to the formation of unique thioetherpyridine products in high yields. These products are versatile and can undergo additional transformations, broadening their synthetic utility. The advantages of this method include a broad substrate scope, mild conditions, and high compatibility with various functional groups.

As the demand for both fluoropharmaceuticals and single enantiomer drugs increases, there is a need for enantioselective synthetic methods toward chiral fluorinated molecules. Trifluoromethyl (CF₃) and the emerging pentafluorosulfanyl (SF₅) fluorinated groups bear characteristic high electronegativity and lipophilicity, while exhibiting distinct steric properties, which make them attractive substituents in drug discovery. Our group's previous exploration of the gold-catalyzed hydration of CF₃- and SF₅-alkynes to furnish the corresponding α-CF₃- and α-SF₅-ketones presents an accessible springboard for the enantioselective synthesis of β-CF₃ and β-SF₅ alcohols. To this end, Noyori–Ikariya asymmetric transfer hydrogenation (ATH) conditions afforded high enantioselectivity (up to 96% ee) and yields (up to 84%) across a scope of eight CF₃ and six SF₅ substrates.

Here is described a theoretical and experimental study of regioselective [4 + 2] Diels–Alder cycloaddition reactions between electron-rich dienes and SF₅-alkynes. These methods give straightforward and convergent access to SF₅-phenols and aminophenols in short reaction sequences. Density functional theory (DFT) calculations combined with reactivity tools, activation strain model, and energy decomposition analysis provide a deeper mechanistic understanding of these Diels–Alder cycloaddition reactions involving an alkyne as a dienophile. We found that regioselectivity and reactivity originate from less destabilizing strain energy and reduced Pauli repulsion between occupied π-orbitals of the diene and dienophile, rather than from stabilizing highest occupied molecular orbital–lowest unoccupied molecular orbital (HOMO–LUMO) interactions. This can be ascribed to a higher degree of asynchronicity in the transition state of the privileged attack of the diene on the dienophile.

We have developed a chiral calcium phosphate-catalyzed transfer hydrogenation of β-trifluoromethylated nitroalkenes. The reaction has a wide substrate scope, giving β-trifluoromethylated nitroalkanes in high yields with high to excellent enantioselectivities (up to 98% ee). Pentafluoroethylated nitroalkene was also a suitable substrate. After the reduction of the nitro group, β-trifluoromethyl amine was synthesized without a loss of enantioselectivity. Chiral 3-trifluoromethyl-2,3-dihydropyrrole derivatives were also synthesized through the intramolecular hydroamination of alkynyl-β-trifluoromethyl amines with high optical purity.

Despite the frequent use of alcohols as solvents in GBB (Groebke–Blackburn–Bienaymé) protocols, the mechanistic reasons for their preference remain poorly understood. In this work, we combined experimental and theoretical investigations to elucidate the roles of solvents and reagents in the GBB reaction, revealing their noninnocent behavior. Kinetic experiments, high-resolution ESI(+)-MS(/MS), and DFT calculations demonstrated that methanol not only acts as a solvent but also as a cocatalyst, significantly influencing the reaction mechanism and accelerating key steps. We proposed both uncatalyzed and PTSA-catalyzed pathways, including alternative mechanisms involving solvent-participating intermediates. The reaction scope confirmed the method’s robustness, and selected fluorescent products were successfully applied as bioimaging probes in live cells. These findings contribute to a deeper understanding of MCR mechanisms and highlight the critical impact of solvent and reagent effects on their efficiency.