Titanocene(III)-Catalyzed Precision Deuteration of Epoxides

Abstract

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 Cp2TiCl2 and (tBuC5H4)2TiCl2 with BnMgBr and PhSiD3 to provide [(RC5H4)2Ti(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.