RESUMEN
Herein, we report the metal-free hydration of pyridine-SF4-alkynes, under acidic conditions and with reaction durations ranging from 5 min to 10 h at room temperature, to synthesize pyridine-SF4-methyl ketones in yields of 59-93%. Further, we demonstrate the synthetic applications of the synthesized pyridine-SF4-methyl ketones, such as chlorination, NaBH4 reduction, Baeyer-Villiger oxidation, and the generation of enol-triflates. These compounds hold promise as useful building blocks in the syntheses of a wide range of SF4-containing drug candidates.
Asunto(s)
Alquinos , Cetonas , Alcoholes , Oxidación-Reducción , PiridinasRESUMEN
The tetrafluoro-λ6-sulfanyl (SF4) moiety has been relatively undeveloped since its discovery in the 1970s. In this study, we synthesized pyridine-SF4-isoxazolines, in which the two heterocycles are connected by a rodlike trans-SF4 linker, via the regioselective 1,3-dipolar cycloaddition of pyridine-SF4-alkynes and nitrones in the presence of triethylamine. SF4 linkers are a viable alternative to para-substituted benzenes, alkynes, and bicyclo[1.1.1]pentyl derivatives in drug design, and pyridine-SF4-isoxazolines have potential applications in drug development.
Asunto(s)
Alquinos , Piridinas , Reacción de CicloadiciónRESUMEN
The trans-tetrafluoro-λ6-sulfanyl (SF4) unit is medicinally attractive because of its high electronegativity, lipophilicity, and unique hypervalent structure. The trans-SF4 unit can characteristically connect two independent molecules linearly. However, there is no example of the use of this unit for medicinal chemistry due to difficulties in synthesis. We report the first synthesis of (ethynyl-trans-tetrafluoro-λ6-sulfanyl)pyridines (t-ethynyl-SF4-pyridines) and their use as versatile reagents for the first direct SF4-alkynylation to carbonyl compounds. The addition reaction of t-ethynyl-SF4-pyridines to the carbonyl group in the presence of MeLi smoothly afforded pyridine-SF4-propargylic tertiary and secondary alcohols in high yields.
Asunto(s)
Alcoholes , Piridinas , Indicadores y ReactivosRESUMEN
Fluoro-functionalization is now recognized as a critical strategy in drug discovery; however, the accessible fluoro-functional groups are limited. We herein introduce an eccentric, fully fluorinated motif, trans-tetrafluoro-λ6-sulfanyl gem-difluorocyclopropene 2. This novel motif is highly lipophilic and polarized, enabling a connection of two independent groups via three continuous atoms with a large angle of pseudo cis configuration. The target motif was synthesized via a [2+1] cycloaddition of electron-deficient (hetero)aryl-SF4-alkynes 1 with an electrophilic difluorocarbene source.