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 o...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2022-02, Vol.61 (6), p.e202114198-n/a
Main Authors: Henriques, Dina Schwarz G., Rojo‐Wiechel, Elena, Klare, Sven, Mika, Regine, Höthker, Sebastian, Schacht, Jonathan H., Schmickler, Niklas, Gansäuer, Andreas
Format: Article
Language:English
Subjects:
Alcohols
Catalysis
Deuteration
Epoxides
mechanism
radicals
Stereoselectivity
titanium
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Summary: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. Titanocene catalysis delivers D to the more substituted C‐atom of epoxides with high efficiency, deuterium incorporation, and stereoselectivity. A novel method of catalyst activation that prevents isotope scrambling warrants the excellent performance of the reaction.
ISSN:1433-7851
1521-3773
1521-3773
DOI:10.1002/anie.202114198