Preparation and Functionalization of Mono‐ and Polyfluoroepoxides via Fluoroalkylation of Carbonyl Electrophiles

Abstract

We outline a new synthetic method to prepare mono-and polyfluoroepoxides from a diverse pool of electrophiles (ketones, acyl chlorides, esters) and fluoroalkyl anion equivalents. The initially formed α-fluoro alkoxides undergo subsequent intramolecular ring closure when heated. We demonstrated the versatility of the method through the isolation of 16 mono-and polyfluoroepoxide products. These compounds provide unique entry points for further diversification via either fluoride migration coupled with ring opening, or defluorinative functionalization reactions, the latter of which can be used as a late-stage method to install select bioactive moieties. The reaction sequences described herein provide a pathway to functionalize the commonly observed products formed from 1,2-addition into carbonyl electrophiles [a] Dr.

Recent Advances in Monofluorinated Carbenes, Carbenoids, Ylides, and Related Species

“…In 2022, Szymczak et al developed a novel reagent for the arylfluoromethylene transfer (Scheme 40). [71] Borazine 107 undergoes addition to ketone 106 followed by fluoride elimination to deliver epoxide 108. The reaction could also be applied to activated carbonyls 106 to obtain bis-addition products 109.…”

A metal-free strategy to construct fluoroalkyl–olefin linkages using fluoroalkanes

“…hexamethylborazine; B 3 N 3 Me 6 ) to stabilize RCF 2 − anions against deuorination. [28][29][30][31][32][33] One class of uorinated compounds that is underdeveloped is aryl/alkyl diuoromethylene containing internal olens. 34 These moieties are an attractive functionality in medicinal chemistry, and are present within marketed drugs such as tauprost and glecaprevir (Fig.…”