ABSTRACT
We describe a titanocene(III)-catalyzed deuterosilylation of epoxides that provides ß-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.
ABSTRACT
A catalytic system for titanocene-catalyzed epoxide hydrosilylation is described. It features a straightforward preparation of titanocene hydrides that leads to a reaction with low catalyst loading, high yields, and high selectivity of radical reduction. The mechanism was studied by a suite of methods, including kinetic studies, EPR spectroscopy, and computational methods. An unusual resting state leads to the observation of an inverse rate order with respect to the epoxide.
