Synthesis of podophyllum lignans via an isolable o-quinonoid pyrone

Abstract

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, H₂/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 Å molecular sieves in tetrahydrofuran. The factors leading to exo-selective additions to α-aryl-o-quinodimethanes are briefly discussed.