We describe atitanocene(III)-catalyzed deuterosilylation of epoxides that provides b-deuterated anti-Markovnikovalcohols with excellent D-incorporation, in high yield, and often excellent diastereoselectivity after desilylation. The key to the success of the reaction is an ovel activation method of Cp 2 TiCl 2 and (tBuC 5 H 4 ) 2 TiCl 2 with BnMgBr and PhSiD 3 to provide[(RC 5 H 4 ) 2 Ti(III)D] without isotope scrambling.Itwas 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.
Here, we describe that polymethylhydrosiloxane (PMHS) is a sustainable terminal reductant in the titanocene catalyzed hydrosilylation of epoxides. The products formally constitute the anti-Markovnikov products of H 2 O-addition to alkenes.PMHS is not only a more sustainable and cheaper reductant than other silanes such as PhSiH 3 and Ph(Me)SiH 2 . It also results in a higher diastereoselectivity of epoxide reduction.
Here, the evolution of the titanocene-catalyzed hydrosilylation of epoxides that yields the corresponding anti-Markovnikov alcohols is summarized. The study focuses on aspects of sustainability, efficient catalyst activation, and stereoselectivity. The latest variant of the reaction employs polymethylhydrosiloxane (PMHS), a waste product of the Müller-Rochow process as terminal reductant, features an efficient catalyst activation with benzylMgBr and the use of the bench stable Cp 2 TiCl 2 as precatalyst. The combination of olefin epoxidation and epoxide hydrosilylation provides a uniquely efficient approach to the formal anti-Markovnikov addition of H 2 O to olefins.
We describe a highly diastereo‐ and enantioselective two‐step formal anti‐Markovnikov addition of H2O to diastereomeric mixtures of trisubstituted olefins. Our approach overcomes the limits of classical stereospecific addition reactions to olefins for the generation of adjacent stereocenters. In these stereospecific reactions, separation of olefin diastereomers is essential. Our method circumvents the need for such difficult separations by simultaneously employing both diastereomeric olefins in the organocatalytic, highly enantioselective, syn‐specific Shi‐epoxidation to yield diastereomeric oxiranes. The stereochemical model proposes the smallest substituent on the olefin to be stereodefining resulting in an identical enantiotopic approach for both olefin isomers on the less substituted carbon. By employing a stereoconverging epoxide hydrosilylation the identically configured center is retained, while the differing one is converted to a planar radical center that is reduced by a syn‐selective intramolecular hydrogen atom transfer (HAT) from a Ti−H bond. The observed converging behavior can be attributed to a HAT‐preceding directional isomerization step, that interconverts the obtained rotameric radicals which ultimately leads to high to excellent enantiomeric ratios of the final secondary alcohols.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.