Synthesis and Use of Trifluoromethylthiolated Ketenimines

Abstract

The synthesis of trifluoromethylthiolated ketenimines is herein described. They are easily synthesized from the corresponding a-trifluoromethylthiolated oximes upon activationw ith triflic anhydride and ab ase. The presumed nitriliumi on resulting from the Beckmann rearrangement is deprotonated to lead to the key intermediate, whose stabilityb rought by the fluorinated substituent was unforeseeable. The reaction of these new building blocks with av ariety of nucleophiles affords av ast array of cyclic and acyclic productsb earing the valuable SCF 3 moiety.

Ketenimines as Intermediates To Access Difluoromethoxylated Scaffolds

“…The postulated key F 2 HCO-bearing ketenimine intermediate was generated in situ from the corresponding oxime probably through a Beckmann rearrangement. Unfortunately, unlike its trifluoromethanesulfanylated analogue, 22 the ketenimine intermediate could never be observed nor isolated, resulting only in the obtention of the corresponding amide upon capture of water. We subsequently decided to test the reactivity of this transient species with nucleophiles.…”

“…We subsequently decided to test the reactivity of this transient species with nucleophiles. Starting with the conditions used for the nucleophilic addition on trifluoromethanesulfanylated ketenimines�2,4,6-collidine (2.0 equiv), Tf 2 O (1.0 equiv) in toluene 22 �various solvents, bases, and reactant stoichiometries were screened (Table 1). Piperidine was chosen as the nucleophile for the optimization as it had proven to give the best results in the case of F 3 CSbearing intermediates.…”

“…As a reminder no such product had been obtained from the reaction with trifluoromethanesulfanylated ketenimines. 22 Besides, the use of alkoxides formed via prior deprotonation with NaH allowed us to increase these yields. After apparent degradation of these products into the corresponding amides during the aqueous workup and over silica, we decided to directly purify the crude materials by column chromatography using basified silica gel, allowing reasonable yields (2l−p, 49− 68%).…”

“…In light of the previous research in our group on trifluoromethane­sulfanylated ketenimines and of the known wide reactivity of ketenimines in general, − we decided to investigate the use of F 2 HCO-bearing ketenimines as key intermediates for the synthesis of valuable motifs such as amidines, imidates, and thioimidates. The interest in the obtained scaffolds is all the more important given the presence of these structures in biologically active molecules. − In fact, ketenimines bearing fluorinated substituents have been underinvestigated.…”

“…Surprisingly, despite the low reactivity of alcohols, their nucleophilic addition was also observed in moderate yields. As a reminder no such product had been obtained from the reaction with trifluoromethane­sulfanylated ketenimines . Besides, the use of alkoxides formed via prior deprotonation with NaH allowed us to increase these yields.…”