Transition-Metal-Free Approach for Z-Vinyl Fluorides by Hydrofluorination of Alkynes bearing SF4 and SF5 Groups.

The synthesis of vinyl fluorides plays a crucial role in various scientific disciplines, including pharmaceutical and materials sciences. Herein, we present a direct and stereoselective hydrofluorination method for the synthesis of Z isomers of vinyl fluorides from alkynes containing unexplored SF5 and SF4 groups. Our strategy employed tetrabutylammonium fluoride (TBAF) as a fluorine source. It demonstrates high compatibility with aryls, biaryls, heteroaryls, and tert-alkyl groups, allowing facile incorporation of SF5 and SF4 groups across the triple bond without any transition-metal catalysts. This approach avoids the potential decomposition of the SF5 or SF4 units via coordination with transition metals or acidic protic sources. Remarkably, this transformation proceeded at room temperature without any additional additives, providing the Z isomer of vinyl fluorides in excellent yield and high selectivity. The presence of a water molecule as a hydrate in TBAF is essential for efficient conversion. This methodology opens new avenues for the synthesis of enchanting SF5 - and SF4 -containing fluorinated vinylic scaffolds, thereby providing advanced opportunities for novel drug discovery and fluorinated polymers.

Regio- and Z-Selective Alkyne Hydroamination and Hydrophenoxylation using Tetrafluoro-λ6 -Sulfanyl Alkynes under Superbasic, Naked Anion Conditions.

Alkyne hydroamination is an effective approach for the production of enamines and enamine-containing N-heterocycles. However, stereoselectivity control is a considerable challenge in this reaction because of the electronic repulsion between an incoming nitrogen lone pair and the alkyne π-system. Herein, we propose a methodology involving ß-regio- and Z-selective alkyne hydroamination by using tetrafluoro-λ6 -sulfanyl (SF4 ) alkynes under superbasic, naked anion conditions. The reaction is compatible with a wide variety of N-heterocycles, including indoles, carbazoles, pyrazoles, and imidazoles, and selectively furnishes SF4 -linked Z-vinyl enamines with ß-regioselectively. Moreover, the method can be extended to the ß- and Z-controlled, base-mediated alkyne hydrophenoxylation with phenols to provide SF4 -linked Z-vinyl ethers in high yields. As the SF4 unit has attracted attention as a bioisostere for alkynes, p-benzenes, bicyclo[1.1.1]pentyl (BCP) groups, and cubanes in medicinal chemistry, this chemistry represents an effective approach to creating novel drug candidates incorporating SF4 -containing molecules.

Synthesis of Pyridine-SF4-Isoxazolines Using the Functionality of trans-Tetrafluoro-λ6-sulfanyl Rodlike Linkers.

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.