New β-amino-α-trifluoromethyl alcohols and their exploration in the synthesis of trifluoromethylated imidazole derivatives

Racemic and enantiomerically pure β-amino-α-trifluoromethyl alcohols were obtained via sequential nucleophilic trifluoromethylation of selected α-imino ketones, derived from arylglyoxals, and subsequent removal of the MeO or Ph(Me)CH substituent, respectively, located at the N-atom. The obtained products, containing a primary amino group, were used for the synthesis of imidazole N-oxides bearing a trifluoromethyl group as a part of the N(1)-alkyl chain. Imidazole N-oxides with an electron-withdrawing ester group at C(4) underwent spontaneous isomerization under the reaction conditions, and the corresponding imidazol-2-one derivatives were isolated as final products

Trifluoromethylation of camphorquinone and its monoimine derivatives

Treatment of (1R)-camphorquinone 2 with (trifluoromethyl)trimethylsilane in the presence of catalytic amounts of caesium fluoride in DME at room temperature yields two pairs of exo/endo isomers of trifluoromethylated silylated alcohols 5 and 6. In this case, nucleophilic addition of the CF3 anion occurs neither regio- nor stereoselectively. On the other hand, the analogous reaction with (1R)-camphorquinone 3-imines 3, followed by hydrolysis with 5 M HCl in ethanol, leads stereoselectively to (1R,2S)-2-hydroxy-2-(trifluoromethyl)bornan-3-one 8. The attempted reductions of the intermediate adducts with NaBH4 in ethanol gave the corresponding (1R,2S)-3-imino-2-(trifluoromethyl)bornan-2-ols 9 as the sole isomers in high yield. The configuration of C(2), that is, the endo course of the nucleophilic CF3 addition, was proven by X-ray crystallography. Furthermore, the reduction of the Cdouble bond; length as m-dashN bond in 9 with DIBAL-H leads stereoselectively to the exo amino derivatives 10, which, by treatment with phosgene, smoothly form the fused 1,3-oxazolidin-2-ones 11. In contrast, the reduction of ketone 8 yields a mixture of the exo,exo- and exo,endo-2,3-diols 12

Advances in Catalytic Enantioselective Fluorination, Mono-, Di-, and Trifluoromethylation, and Trifluoromethylthiolation Reactions

Fluorine is the most electronegative element in the periodic table, and the introduction of one or more fluorine atoms into a molecule can result in greatly perturbed properties. Methods to introduce fluorine into small organic molecules have been actively investigated for many years by specialists in the field of fluorine chemistry. The earliest advances in catalytic asymmetric fluorination were made by exploiting transition metal enolates, capable of a bidentate mode of coordination to a metal. In 2002, Sodeoka and coworkers reported the enantioselective fluorination of β-ketoesters catalyzed by a chiral palladium complex. In 2005, Shibata and co-workers reported enantioselective chlorination and fluorination of carbonyl compounds capable of two-point binding. In 2011, Gade and co-workers described the synthesis of a new class of chiral tridentate N-donor pincer ligands, bis(oxazolinyl-methyldiene)isoindolines