Regioselective Deuteration of a 3,4-Dialkoxypyrroline N-Oxide and Synthesis of 8a-d-Indolizidines

A simple and efficient method for C-2 deuterium labeling of 3,4-di-tert-butoxypyrroline N-oxide, a useful chiral building block in azaheterocycles syntheses, is presented. Selective and quantitative deuterium incorporation (> 99 %) was achieved by base-catalyzed H/D exchange in D2O under mild reaction conditions. A mechanistic pathway based on kinetic and computational data was proposed. The labeled nitrone was used in the synthesis of C-8a deuterated (1R,2R,8aR)-lentiginosine.