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 an Eccentric Electron-Deficient Fluorinated Motif, Tetrafluoro-λ6-sulfanyl gem-Difluorocyclopropenes.

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.

An eccentric rod-like linear connection of two heterocycles: synthesis of pyridine trans-tetrafluoro-λ6-sulfanyl triazoles.

The trans-tetrafluoro-λ6-sulfane (SF4) group has been utilized as a unique three-dimensional building block for the linear connection of two independent N-heterocycles, pyridines and triazoles. The linearly connected heterocyclic compounds were synthesized by thermal Huisgen 1,3-dipolar cycloaddition between previously unknown pyridine SF4-alkynes and readily available azides, providing a series of rod-like SF4-connected N-heterocycles in good to excellent yields. X-ray crystallographic analysis of the target products revealed the trans-geometry of the SF4 group, which linearly connects two independent N-heterocycles. This research will open the field of chemistry of SF4-connected heterocyclic compounds.