CHIRAL SYNTHONS FROM CARVONE - PART 31 - ENANTIOSPECIFIC TOTAL SYNTHESIS OF (-2-PUPUKEANONE AND 5-EPI-2-PUPUKEANONE())

The first enantiospecific total synthesis of (+)-2-pupukeanone and 5-e pi-2-pupukeanone has been achieved starting from (R)-carvone, employin g 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. Ozon olytic cleavage of the exomethylene moiety, dehydration of the tertiar y alcohol and regioselective Wolff-Kishner reduction transforms the is otwistanes 19 and 20 into the enone 24, Alternatively, kinetic alkylat ion of the bicyclo[2.2.2]octenone 12 with 1,4-dibromo-2-methylbut-2-en e followed by 5-exo-trig allyl radical cyclisation of 35 and selective functional group transformations generates the isotwistane 23 and a m inor amount of the rearranged product 29. Finally, catalytic hydrogena tion transforms the enone 24 into (+)-2-pupukeanone 5 and its C-5 epim er 6.