Abstract
Abstract This thesis reports on a second synthetic generation approach towards cis-clerodane diterpenoids (±)-6□-acetoxy-2-oxokolavenool (51). The key step of this approach is the Diels-Alder cycloaddition of dienophile 60 with trans-piperylene. Dienophile 60 was synthesized efficiently starting from 3-ethoxy-6-methyl-2-cyclohexenone (45). Alkylation followed by reduction and acid hydrolysis gave enone 63 (scheme 11). Cyano ketone 66 was then synthesized from enone 63 using an established sequence of reactions. Dehydrogenation of cyano ketone 66 then furnished the desired dienophile 60. Diels-Alder cycloaddition of enone 60 with trans-piperylene gave cycloadduct 61 in synthetically useful yields, which was subsequently subjected to reductive alkylation conditions to give bicyclic ketone 68. Conjugate addition of lithium dimethylcuprate upon ketone 68 then resulted in bicyclic ketone 69 which was treated under standard Wacker oxidation reaction conditions to furnish diketone 74. Keto alcohol 75 was then synthesized by treating diketone 74 with vinylmagnesium bromide. The final target diol 72 was then achieved by reduction of keto alcohol 75 with lithium aluminum hydride. Keto alcohol 75 has been previously utilized as the key intermediate in a reported total synthesis of (±)-6□-acetoxy-2-oxokolavenool (51). The details of our investigation towards the synthesis of keto alcohol 75 are described in this thesis.