Diels–Alder additions to 1-phenyl-2-benzopyran-3-one and transformations of the adducts: model experiments for podophyllotoxin synthesis

Abstract

1-Phenyl-2-benzopyran-3-one 2 adds to a series of unsymmetrically substituted dienophiles (methyl acrylate, ethyl crotonate, methyl ω-bromocrotonate, and crotonaldehyde) with regioselectivity largely determined by the phenyl group but with little endo-exo-selectivity. Addition of 2 to dimethyl fumarate results in preferred exo-addition adjacent to the phenyl group. The stereochemistry of hydrogenolysis of the endo15 and exo16 maleate adducts of 2 appears to be governed by steric effects rather than the nature of the catalyst (Pd or Ni). Catalytic hydrogenation of the cis dihydronaphthalenes 23 and 24 gave 18 and 25, respectively, which were different from the products obtained by addition of the o-quinodimethanes 11 and 12 to dimethyl maleate in agreement with preferred exo-addition in both Diels–Alder reactions. The steric course of catalytic hydrogenation of the trans-1,2-dihydronaphthalenes 26 and 28 and the carboxylic acid 31 is controlled by the 1-phenyl and 1-carboxy group, respectively, rather than by the 2-substituent.