Chiral synthons from carvone. 9. Radical annulation strategy to chiral pupukeanones: total synthesis of (+)-10-exo-(1-naphthyl)pupukean-9-one and (+)-10-exo-(1-naphthyl)-5-epipupukean-9-ones

Intramolecular alkylation reaction of the bromoenone 12, obtained from S-carvone in three steps furnished the bicycle[2.2.2] octenone 13. Contrary to the anticipated radical annulation reaction, the bicyclic bromides 14 and 15, obtained from the enone 13, generated exclusively the cyclopropane product 18 via a 3-exo trig radical cyclization on reaction with nBu3SnH and AIBN, even in the presence of a large excess of a radicophile. On the other hand, bromoenone 24, synthesized from R-carvone via S-naphthylcarvone 21, underwent radical annulation reaction in the presence of radicophiles to furnish the isotwistanes 25-28 in a regio- and stereospecific manner. Hydrogenation of the olefin 34, obtained from the diketone 27 via a regiospecific Wittig reaction, furnished the naphthyl-5-epipupukean-9-one 33, whereas stereoselective hydrogenation of the enone 36, prepared from the keto ester 25 via a Grignard reaction and dehydration sequence, generated the naphthylpupukeanone 32