The Ring-Opening Reaction of 3,3,3-Trifluoropropene Oxide with Carbanions: Reaction of α-Cyanocarbanions

Abstract

Nucleophilic ring-opening reaction of 3,3,3-trifluoropropene oxide (TFPO) was studied. Reaction of TFPO with carbanions stabilized by cyano group gave γ-cyanohydrins in moderate to good yields. Meanwhile, reaction of the carbanions from malonic ester and nitromethane resulted in recovery of TFPO.

General Syntheses of Optically Active α-Trifluoromethylated Amines via Ring-Opening Reactions of N-Benzyl-2-trifluoromethylaziridine

“…Of course, some epoxides and aziridines, especially those containing electron-withdrawing groups, are known to be reactive toward nucleophiles. ,, Preliminary MO calculations of the trifluoromethylated aziridines 1 predicted higher reactivity of the fluorinated aziridine to nucleophiles due to a higher positive charge on its methylene carbon, a much more polar β-carbon−nitrogen bond, and a much lower LUMO level, compared with nonfluorinated methylaziridine and 2,3-epoxy-1,1,1-trifluoropropane. Thus, we initially considered 2-trifluoromethylated aziridine ( 1 ) would be somewhat reactive toward nucleophiles; however, this was contrary to the present experimental results.…”

“…In contrast, ring-opening reactions of the trifluoromethylated epoxide proceeded quite smoothly. 2,3-Epoxy-1,1,1-trifluoropropane reacted vigorously with alkoxides to form polymers, with amines to yield trifluoromethylated amino alcohols, and with cyano-stabilized carbanions to make γ-cyanohydrins . On the other hand, the epoxide was inert toward malonate and nitro group stabilized carbanions.…”

“…We have reported the ring-opening reactions of the trifluoromethylated epoxide with carbanions to be difficult. Although the 2,3-epoxy-1,1,1-trifluoropropane was ring-opened smoothly by α-cyano carbanions generated from substituted acetonitriles, the compound was inert toward both the malonate carbanion and nitromethane carbanion . Though the trifluoromethyl group of the epoxide should electronically activate the epoxide via its strong electron-withdrawing effect, the reaction should be prevented by electrostatic repulsion between lone pairs of fluorine on the trifluoromethyl group and the negative charge of nucleophiles.…”

1,1,1-Trifluoro-2,3-epoxypropane

“…32,40 The carbanions from substituted acetonitriles give cyanohydrins (eq 26). 44 The diastereoselectivity of the reaction is low. While further ring-closure reaction to cyclopropanes via cyanostabilized carbanion is highly diastereoselective (eq 27).…”

“…42The Ring-opening Reaction of TFPO with Carbon Nucleophiles. Similar to nucleophilic ring-opening reactions of other epoxides, 43 a few carbon nucleophiles [cyanide (eq 24), 5b substituted acetonitriles,44 and Grignard reagents 45 ] yield ring-opening products from TFPO directly without additional Lewis acid catalyst. Simple reactions of TFPO with Grignard reagents give a certain amount of halohydrns.…”