ACS Organic & Inorganic Au最新文献

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.