The hydroamination of TIPS-C≡C-SF5 – A bench-top route to pentafluorosulfanylated enamines

Abstract

Synthetic access to a variety of aliphatic and vinylic pentafluorosulfanylated building blocks remains a major challenge in contemporary organofluorine chemistry hampering its broad investigation in the context of medicinal chemistry, agrochemistry and functional materials. Herein, we report a bench-top protocol to access the virtually unknown class of a-SF5-enamines under rather benign reaction conditions. This reaction combines the in-situ protodesilylation of the commercially available precursor TASP with the unprecedented hydroamination of HC≡C-SF5. The on-site use of highly toxic gases is completely avoided, granting access to a-SF5-enamines to conventional labs. Furthermore, employing a combined experimental and computational approach, we revealed a two-step cascade reaction. The excellent E-diastereoselectivity of the reaction is suggested to be the result of the convergence of the fast Z-/E- isomerization of a vinyl anion as well as isomerization of the iminium ion in the equilibrium. The remarkably thermal stability of these SF5-enamines encourages further studies of its synthetic utility.

The hydrothiolation of TIPS-CΞC-SF5 – Charting the chemical space of beta-SF5 vinyl sulfides

“…Surprisingly, aromatic amino (3) and hydroxy (10) substituents did not interfere with the reaction at all but resulted in superior yields due to its strongly electron donating character. In contrast, moderately electron withdrawing substituents like CF3 (12,13,17) as well as unprotected carboxylic acids ( 25) caused a slight reduction in yield. The even stronger -accepting nitro group was found to significantly harm the reaction when in close proximity to the reaction site (11) (33%) (Figure 2) while it was smoothly tolerated in a remote position (20).…”

“…[13] A broad variety of so far elusive -SF5 enamines could be obtained in moderate to excellent yields employing a rather simple bench-top procedure. [13] Inspired by these findings, we became interested in the ability of thiols as S-nucleophiles to undergo an analogous hydrothiolation reaction. Such a reaction would allow us to access the corresponding vinyl sulfides paralleling the chemistry of -substituted acetylenes.…”

“…[12] Very recently, we reported the hydroamination of TIPS-CC-SF5 (1) in a proof of principle study to showcase the versatility of this molecule. [13] A broad variety of so far elusive -SF5 enamines could be obtained in moderate to excellent yields employing a rather simple bench-top procedure. [13] Inspired by these findings, we became interested in the ability of thiols as S-nucleophiles to undergo an analogous hydrothiolation reaction.…”