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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 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.

SUBMITTER: Henriques DSG

PROVIDER: S-EPMC9305931 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Titanocene(III)-Catalyzed Precision Deuteration of Epoxides.

Henriques Dina Schwarz G DSG Rojo-Wiechel Elena E Klare Sven S Mika Regine R Höthker Sebastian S Schacht Jonathan H JH Schmickler Niklas N Gansäuer Andreas A

Angewandte Chemie (International ed. in English) 20211221 6

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] ...[more]

PMID: 34845824

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