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

Abstract

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.