Benzylamine As Hydrogen Transfer Agent:Cobalt-catalyzed Chemoselective C=C Bond Reduction Of ?-trifluoromethylated ?,?-unsaturated Ketones Via 1,5-hydrogen Transfer

The incorporation of fluorine-containing groups into an organic molecule can bring about some remarkable changes in the physical properties,chemical reactivity,and biological activity of the derived fluorinated compounds.The trifluoromethyl group(CF₃)is the most widely used fluorine-containing group owing to its strong electron-withdrawing power and high lipophilicity.?-CF₃ saturated ketones are very important motifs,which are often found in biologically active compounds.And it is difficult to directly introduce trifluoromethyl at?-position of a carbonyl group to construct?-CF₃-saturated ketones.?-CF₃-Substituted enones can be used to access?-CF₃ saturated ketones,which is generally regarded as an efficient pathway.So far,it was reported that?-CF₃ saturated ketones were synthesized via conjugate addition or via reduction of the carbonyl groups followed by isomerization in two-pot catalytic reactions from?-CF₃-Substituted enones.However,the chemoselective reduction of the C=C bond of?-CF₃-substituted enones has not been reported.Herein,we present a Lewis acid catalyzed chemoselective C=C bond reduction of?-CF₃?,?-unsaturated ketones with benzylamine,as a novel synthetic route to?-trifluoromethyl carbonyl compounds.The specific work is as follows:We developed an efficient cobalt-catalyzed chemoselective reduction of?-CF₃-?,?-unsaturated ketones using benzylamine as hydrogen transfer agent involving intramolecular 1,5-hydrogen transfer.Firstly carefull screenings of the Lewis acid,the substituted benzylamine,solvent and reaction temperature were carried out and the optimal reaction conditions were found as following:2 mol%Co(Cl O₄)₂·6H₂O as a catalyst and 3 equiv Bn NH₂ as a reducing agent,in toluene at 100 ^oC for 24 h.The reaction proceeded smoothly with a relatively wide range of substrates including those bearing aromatic heterocycles such as a furyl ring system in good yields(70–92%).This provides an efficient method for the synthesis of?-CF₃ saturated ketones in one-pot.This methodology was also applied to the selective C=C reduction of other enone substrates bearing no?-CF₃-substituent,of which?-substituted or?,?-disubstituted enones are tolerated,giving the desired products in good yields(72–75%).Finally,a possible catalytic mechanism has been proposed.Mechanistic studies indicate that the reaction involves1,5-hydrogen transfer.