Titanocene(III)-Catalyzed Precision Deuteration of Epoxides

We describe a titanocene(III)-catalyzed deuterosilylation of epoxides that provides β-deuterated anti-Markovnikov alcohols with excellent D-incorporation, in high yield, and often excellent diastereoselectivity after desilylation. The key to the success of the reaction is a novel activation method of Cp₂ TiCl₂ and (tBuC₅ H₄ )₂ TiCl₂ with BnMgBr and PhSiD₃ to provide [(RC₅ H₄ )₂ Ti(III)D] without isotope scrambling. It was developed after discovering an off-cycle scrambling with the previously described method. Our precision deuteration can be applied to the synthesis of drug precursors and highlights the power of combining radical chemistry with organometallic catalysis.