Hexafluoroacetone: An appealing key player in organic chemistry

Abstract

(A) Synthesis of Quinolines: Uneyama and co-workers developed the one-pot synthesis of highly bioactive quinolines. Pentafluoropropen-2-ol (PFP) formed from HFA facilitates the synthesis of substituted quinolines via tandem Mannich addition Friedel Crafts cyclization aromatization followed by nucleophilic defluorinative substitution. (FIGURE) (B) Synthesis of Fluoro-Substituted Pipecolic Acids: Burger and co-workers reported a new route for the synthesis of substituted pipecolic acids from hexafluoroacetone-protected (S)- glutamic acid. Pipecolic acids can be used as investigative tools for the cistrans isomerization of the peptide bond as well as protein folding. (FIGURE) (C) Stereoselective Synthesis of Spirophosphoranes: Highly stereoselective tricyclic phosphoranes were prepared by the group of Mironov by reacting dioxaphosphole with hexafluoroacetone. (FIGURE) (D) Approach to Depsipeptides: Gulevich et al. has reported a high-yielding synthetic approach for the synthesis of depsipeptides via Passerini three-component condensation of isocyanide, carboxylic acid and hexafluoroacetone. (FIGURE) (E) Oxetane Formation: Petrov et al. reported the cycloaddition of quadricyclanes and HFA to give oxetanes which are stable in both acidic and basic medium. (FIGURE) (F) Preparation of Hexafluoroisopropanol-Functionalized Derivatives: Recently, Sridhar et al. used hydrated hexafluoroacetone for an efficient carbonyl-ene reaction with alkenes having allylic hydrogens. (G) Lactone and Amide Formation: The reactions of β-hydroxy acids with HFA and carbodiimide have been used to obtain carboxy-activated six-membered lactones in good yields which in turn afforded the corresponding amides. (FIGURE) (H) β-Hydroxy-β- bis(trifluoromethyl)imines: In an enamine-mediated addition, selected imines with HFA gave the corresponding β-hydroxy-β-bis(trifluoromethyl)imines in good to excellent yields. These imines are versatile synthons for the synthesis of bioactive compounds. © Georg Thieme Verlag Stuttgart - New York.