A Concise Synthesis of (-)-Aplyviolene Facilitated by a Strategic Tertiary Radical Conjugate Addition

摘要

Aplyviolene (1) and macfarlandin E (2, Scheme 1 A) are representative of the more complex members of the rearranged spongian diterpene class of natural products. These diterpenes are structurally defined by attached cis-perhy-droazulene and 6-acetoxy-2,7-dioxabicyclo3.2.1octan-3-one fragments. The substantial challenge in assembling these structures centers on the construction of the sensitive bicyclic lactone subunit and the formation of the C8-C14 o-bond joining the two ring systems, a challenge augmented by the quaternary nature of C8. We previously reported preparation of the lactone subunits of 1 and 2 by the synthesis of truncated congeners 3 and 4 (Scheme 1 A), as well as the first total synthesis of aplyviolene (outlined in Scheme 1B). In this latter effort, the key C8-C14 σ-bond was formed by Michael addition of tertiary enolate 5 to enone 6. Subsequent elaboration of product 7 provided intermediate 8, which was converted to (—)-aplyviolene along the lines of our earlier synthesis of 3. Undesirable aspects of this first-generation synthesis are the lengthy preparation of the cis-perhydroazulene unit and the need to remove the extraneous ketone carbonyl group from the product of the fragment-coupling step.