A Five-Membered Enantiopure Cyclic Nitrone from Malic Acid by Regioselective Oxidation of Cyclic Hydroxylamine. Synthesis of (1S,7S,8aR)-Octahydro-1,7-dihydroxyindolizine

Abstract

The chiral optically pure five-membered 3-tert-butoxy-1-pyrroline N-oxide (1) was synthesized by\na convenient five-step procedure from diethyl L-malate. The key step is the regioselective HgO\ndehydrogenation of the N-hydroxypyrrolidine 6 obtained by double-nucleophilic displacement of a\n(bis)mesylate with hydroxylamine. A rationalization of the observed regioselectivity of the oxidation\nby studying the oxidation of a deuterated N-hydroxypyrrolidine 20 is reported. Nitrone 1 has been\napplied to the synthesis of a new (lS,7S,8aR)-1,7-dihydroxyindolizidin(e2 8) via 1,3-dipolar\ncycloaddition strategies.