SYNTHESIS OF PODOPHYLLUM LIGNANS VIA AN ISOLABLE O-QUINONOID PYRONE

The 2-benzopyran-3-one 10 is a stable, isolable and useful Diels-Alder diene; its methyl 4-benzoyloxycrotonate adduct 23 formed regioselectively and stereoselectively in acetonitrile is reduced with H-2/Pd to give 31 with inversion of C-1-stereochemistry. The latter is readily converted into methyl podophyllate 34 (Scheme 2) which is directly lactonised to podophyllotoxin using ZnCl2/4 angstrom molecular sieves in tetrahydrofuran. The factors leading to exo-selective additions to alpha-aryl-o-quinodimethanes are briefly discussed.