Chiral synthons from carvone. Part 31. Enantiospecific total synthesis of (+)-2-pupukeanone and 5-epi-2-pupukeanone

Abstract

The first enantiospecific total synthesis of (+)-2-pupukeanone and 5-epi-2-pupukeanone has been achieved starting from (R)-carvone, employing a radical cyclisation reaction based approach. (R)-Carvone has been transformed into the bicyclo[2.2.2]octenone 12 via kinetic alkylation, bromination of the isopropenyl moiety and intramolecular alkylation, which on further alkylation with prenyl bromide leads to bicyclo[2.2.2]octenone 16. The 5-exo-trig radical cyclisation of the bromohydrin 17, obtained from 16, furnishes an epimeric mixture of the isotwistanes 19 and 20 along with a minor amount of the rearranged product 21. Ozonolytic cleavage of the exomethylene moiety, dehydration of the tertiary alcohol and regioselective Wolff-Kishner reduction transforms the isotwistanes 19 and 20 into the enone 24. Alternatively, kinetic alkylation of the bicyclo[2.2.2]octenone 12 with 1,4-dibromo-2-methylbut-2-ene followed by 5-exo-trig allyl radical cyclisation of 35 and selective functional group transformations generates the isotwistane 23 and a minor amount of the rearranged product 29. Finally, catalytic hydrogenation transforms the enone 24 into (+)-2-pupukeanone 5 and its C-5 epimer 6.