Asymmetric synthesis XXVIII: Hydroxylated benzoquinolizidine analogues of podophyllotoxin via the CN(R,S) method

Article abstract of DOI:10.1016/S0040-4020(01)89913-0

The condensation of 2-cyano-6-phenyloxazolopiperidine synthon (-)-5 with piperonal, gave after reduction, the optically pure pivotal amino-alcohol 8. Two strategies were developed to prepare the epimeric azapodophyllotoxin analogues 2 and 3 via Grignard reactions on an iminium ion generated from the common intermediate 8. The first strategy was based on an intramolecular reaction while the second involved a stereocontrolled addition reaction on iminium ion 20.