Synthesis of Isopalhinine A and Palhinine D
Biomimetic Syntheses of (±)-Isopalhinine A, (±)-Palhinine A, and (±)-Palhinine D.
Angew. Chem. Int. Ed. 2018;
14 December 2018 (online)
Key wordsLycopodium alkaloids - (±)-isopalhinine A - (±)-palhinine D - Claisen rearrangement - oxidative dearomatization - Diels–Alder reaction - acyl radical cyclization
Isopalhinine A and palhinine D are Lycopodium alkaloids with highly bridged carbon frameworks that incorporate a 5/6/6 tricycle along with a hemiaminal moiety. Hsieh and co-workers report concise syntheses of both alkaloids, which rely on an oxidative dearomatization/[4+2] cycloaddition strategy to construct the bicyclo[2.2.2]octane core.
9-exo-Tet cyclization of D under basic conditions furnished the azonane ring in E. Subsequent oxidation with hypervalent iodine gave a masked ortho-benzoquinone intermediate that underwent Diels–Alder reaction with acrolein to afford F. Employing Tomioka’s method, acyl radical cyclization of aldehyde I furnished the characteristic isotwistane core in K.