Addition of silyloxydienes to 2,6-dibromo-1,4-benzoquinone: an approach to highly oxygenated bromonaphthoquinones for the synthesis of thysanone

The synthesis of tetraoxygenated bromonaphthoquinones , , , , key intermediates for a synthesis of the 3C protease inhibitor, thysanone, were investigated. Addition of 1-methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadiene to 2,6-dibromo-1,4-benzoquinone in benzene afforded a mixture of naphthoquinone , arising from Diels–Alder addition followed by aromatisation, and Michael adduct . The Michael adduct predominated when THF was used as solvent whereas predominated when benzene was used. Naphthoquinone underwent benzylation to naphthoquinone . Addition of 1,1-dimethoxy-3-trimethylsilyloxy-1,3-butadiene to 2,6-dibromo-1,4-benzoquinone followed by benzylation failed to afford the desired bromonaphthoquinone yet methylation did afford naphthoquinone . Bromonaphthoquinone was finally prepared from naphthol , obtained from addition of diene to 1,4-benzoquinone , followed by ortho-bromination and oxidation. Attempted Sakurai allylation of bromonaphthoquinone afforded naphthodihydrofuran . A similar observation was observed for 2-carbomethoxy-1,4-naphthoquinone that also underwent Sakurai allylation to afford naphthodihydrofuran . The structure of Michael adduct was confirmed by X-ray crystallography.