Regio‐ and <i>Z</i>‐Selective Alkyne Hydroamination and Hydrophenoxylation using Tetrafluoro‐λ<sup>6</sup>‐Sulfanyl Alkynes under Superbasic, Naked Anion Conditions
Trapti Aggarwal, Kenshiro Hada, Yusuke Murata, Yuji Sumii, Kazuhiro Tanagawa, Kiyoteru Niina, Soichiro Mori, Jorge Escorihuela, Norio Shibata
Abstract
Abstract 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‐λ 6 ‐sulfanyl (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 4 ‐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 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.