Total Synthesis of (±)-Crokonoid A
We report herein a total synthesis of crokonoid A, featuring a dually bridged 6/7/6/5-fused tetracyclic carbon framework incorporating an unprecedented tricyclo[4.4.1.11,4]dodecane-2,11-dione core. The synthesis is highlighted by the following key transformations: (a) a regioselective decarboxylative allylation of a 1,3-dienyl carbonate to furnish an α-allyl-β,γ-unsaturated ketone; (b) a domino sequence involving ozonolysis, intramolecular aldol reaction, and acetalization to construct the bicyclo[4.3.1]decanedione core from a fused ring system, in which the acetalization step effectively stabilized the otherwise unstable aldol intermediate; (c) a palladium-catalyzed intramolecular cycloalkenylation of a ketone to assemble the bicyclo[3.2.1]octanedione system, in which the hybridization state of the neighboring carbon proved crucial for the success of this cyclization; and (d) SmI2–HMPA-mediated regio- and stereoselective reduction of the C14 ketone.
École Polytechnique Fédérale de Lausanne
École Polytechnique Fédérale de Lausanne
École Polytechnique Fédérale de Lausanne
2025-09-26
jacs.5c14479
REVIEWED
EPFL