Sandwich Diimine-Copper Catalyzed Trifluoroethylation and Pentafluoropropylation of Unactivated C(sp3)-H Bonds by Carbene Insertion

We report here sandwich-diimine copper complex-catalyzed trifluoroethylation and pentafluoropropylation of unactivated C(sp(3))-H bonds in alkyl esters, halides, and protected amines by employing CF3CHN2 and CF3CF2CHN2 reagents. Reactions proceed in dichloromethane solvent at room temperature. Identical C-H functionalization conditions and stoichiometries are employed for generality and convenience. Selectivities for C-H insertions are higher for compounds possessing stronger electron-withdrawing substituents. Preliminary mechanistic studies point to a mechanism involving a pre-equilibrium forming a sandwich-diimine copper-CF3CHN2 complex followed by rate-determining loss of nitrogen affording the reactive copper carbene. It reacts with trifluoromethyldiazomethane about 6.5 times faster than with 1-fluoroadamantane explaining the need for slow addition of the diazo compound.

Automated summary

In this study, trifluoroethylation and pentafluoropropylation reactions of unactivated C(sp(3))-H bonds in alkyl esters, halides, and protected amines were catalyzed by sandwich-diimine copper complex. The reactions took place in dichloromethane solvent at room temperature. Compounds with stronger electron-withdrawing substituents showed higher selectivities for C-H insertions. Preliminary mechanistic studies suggested that the reaction mechanism involves the formation of a pre-equilibrium sandwich-diimine copper-CF3CHN2 complex, followed by rate-determining loss of nitrogen to generate the reactive copper carbene. The carbene reacted with trifluoromethyldiazomethane much faster than with 1-fluoroadamantane, explaining the need for slow addition of the diazo compound.