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 β‐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 β‐regioselectively. Moreover, the method can be extended to the β‐ 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.

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.

Pyridine-tetrafluoro-λ6-sulfanyl-alkynes have emerged as building blocks for synthesizing linearly-linked pyridine-heterocycles. They are prepared via a two-step procedure comprising the radical addition of pyridine-tetrafluoro-λ6-sulfanyl-chlorides and alkynes and subsequent base-promoted elimination of HCl. Herein we developed a straightforward alternative synthesis via the radical coupling of pyridine-tetrafluoro-λ6-sulfanyl-chlorides with ethynylbenziodoxolone reagents under LED irradiation.

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Alkyne hydroamination is an effective approach for the production of enamines and enaminecontaining 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 β-regio-and Zselective alkyne hydroamination by using tetrafluoro-λ 6sulfanyl (SF 4 ) 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 SF 4linked Z-vinyl enamines with β-regioselectively. Moreover, the method can be extended to the β-and Zcontrolled, base-mediated alkyne hydrophenoxylation with phenols to provide SF 4 -linked Z-vinyl ethers in high yields. As the SF 4 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 SF 4 -containing molecules.