A five-membered enantiopure cyclic nitrone from malic acid by regioselective oxidation of cyclic hydroxylamine. Synthesis of (1S,7S,8aR)-octahydro-1,7-dihydroxyindolizine

Article abstract of DOI:10.1021/jo00120a016

The chiral optically pure five-membered 3-tert-butoxy-1-pyrroline N-oxide (1) was synthesized by a convenient five-step procedure from diethyl L-malate. The key step is the regioselective HgO dehydrogenation of the N-hydroxypyrrolidine 6 obtained by double-nucleophilic displacement of a (bis)mesylate with hydroxylamine. A rationalization of the observed regioselectivity of the oxidation by studying the oxidation of a deuterated N-hydroxypyrrolidine 20 is reported. Nitrone 1 has been applied to the synthesis of a new (1S,7S,8aR)-1,7-dihydroxyindolizidine (28) via 1,3-dipolar cycloaddition strategies.