Work

Total Synthesis of (±)-Crokonoid A

Year: 2025

Type: article

Abstract: 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[4.4.1.1 1,4 ]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) SmI 2 –HMPA-mediated regio- and stereoselective reduction of the C14 ketone.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.5c14479

Authors: Dan Forster, Qian Wang, Jieping Zhu

Institution: École Polytechnique Fédérale de Lausanne

Language: English

Topic: Organic Chemistry Synthesis Methods

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: École Polytechnique Fédérale de Lausanne, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

Award: Ynimines and Isocyanides: From Methodology Development to Natural Product Synthesis