Robust Continuous-Flow Synthesis of Deuterium-Labeled <i>β</i>-Nitroalcohols Catalyzed by Basic Anion Exchange Resin
Tsuyoshi Yamada, Kwihwan Park, Naoya Ito, Hayato Masuda, Wataru Teranishi, Sunliang Cui, Hironao Sajiki
Abstract
Abstract A practical and efficient continuous-flow system was developed for the synthesis of site-selectively deuterium-labeled β-nitroalcohols by using the tertiary amine-functionalized basic anion exchange resin, WA30, as a heterogeneous organocatalyst. For this system, WA30 was prepacked in a cartridge under metal-free conditions. The system was operated by pumping a solution of aldehydes or ketones, as electrophiles, and nitroalkanes in a solvent system of deuterium oxide and THF in the catalyst cartridge. Various deuterated β-nitroalcohols were obtained in moderate to excellent yields with high deuteration efficiencies. The continuous-flow system was applied in continuous synthesis for at least 72 h without degradation of the heterogeneous organocatalyst activity.