Stereoselective approach to hydroxyindolizidines: Protection/deprotection of the nitrone functionality via cycloaddition/retrocycloaddition

[GRAPHICS] The enantiomerically pure Indolizidine (-)-21 has been synthesized starting from L-malic acid. The key intermediate 20 has been assembled through an i ntramolecular 1,3-dipolar cycloaddition of a nitrone generated in situ by r etrocycloaddition from isoxazolidine 17 or 18. The configuration of the new three stereocenters was set up with complete control in the cycloaddition step, The presented synthetic route provides a general and highly selective methodology toward indolizidines having the [1,8a]-cis configuration.