Installation of Trifluoromethylated Quaternary Carbon Stereocenters via Asymmetric Epoxidation of Tetrasubstituted Alkenes

The construction of vicinal quaternary carbon centers via epoxidation of tetrasubstituted alkenes remains a formidable challenge in asymmetric synthesis. Herein, a first catalytic enantioselective epoxidation of acyclic tetrasubstituted alkenes is reported, prepared through the Knoevenagel condensation of trifluoromethyl ketones with malononitrile. (S)- and (R)-configured epoxides are obtained in generally excellent yields (up to 98%) and with good to high enantioselectivities (up to 89% ee), employing a commercially available system, comprising Takemoto's catalysts and tert-butyl hydroperoxide (TBHP). Highly reactive new tetrasubtituted alkenes allow the first successful use of Takemoto's catalyst under oxidative conditions. Interestingly, density functional theory studies show that TBHP is exclusively activated by the amino thiourea, with halogen-bonding interactions playing a critical role in affecting the stereochemical outcome of the epoxidation. Derivatizations provide access to densely functionalized trifluoromethylated compounds, featuring one or two vicinal carbon quaternary stereocenters, with the second center being introduced in a highly stereoselective manner.