Synthesis of Chiral α-CF 3 -Substituted Benzhydryls via Cross-Coupling Reaction of Aryltitanates

We describe a highly efficient approach toward α-CF -substituted benzhydryls thanks to the employment of organotitanium(IV) based nucleophiles. The use of commercially available anesthetic halothane as a cheap fluorinated building block in a sequential one-pot nickel-catalyzed enantioselective cross-coupling reaction of aryl titanates allowed for the synthesis of chiral α-CF -substituted benzhydryls in good yields and excellent enantioselectivities. Alternatively, α-CF -benzyl bromides could be employed under similar conditions to obtain the same family of compounds in higher yields and excellent selectivities. A benzhydryl moiety is a common motif in many biologically active compounds, and their enantioenriched fluorinated analogs should be of great interest in the search for novel drugs and agrochemicals.