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Organic Chemistry Highlights

Total Synthesis

Monday, November 6, 2023
Douglass F. Taber
University of Delaware

The Jia Synthesis of Aberrarone

The tetraketone aberrarone (3), isolated from the feathery Caribbean gorgonian Pseudopterogorgia elisabethae, shows in vitro activity against the malaria parasite. Yanxing Jia of Peking University devised a route to 3 based on the oxidative radical cyclization of 1 to 2 (J. Am. Chem. Soc. 2023, 145, 9459. DOI: 10.1021/jacs.3c02511).

The eneyne sidechain of 1 was prepared from the commercial chloride 3. Cu-catalyzed coupling with the Grignard reagent 4 led to the diyne 5. Hydrozirconation followed by iodination then gave 6.

The synthesis began with commercial (S,S)-carveol (7). Diastereoselective hydroboration led to the diol 8, that was selectively converted to the iodide 9. Remarkably, direct coupling of 9 with the alkenyl iodide 6 followed by oxidation led cleanly to the desired 10. Acylation with 11 then completed the assembly of 1.

Oxidation of the 1,3-diketone 1 with Mn(OAc)3 would initially give the radical 12. The cascade radical cyclization followed, leading with high diastereocontrol to the tetracyclic ketone 2.

Desilylation of the diketone 2 gave the diene 13. Selective epoxidation followed by periodate cleavage led to the triketone 14. Hydrogenation gave 15, that was oxidized to the tetraketone aberrarone (3).

It is instructive to compare this synthesis with that reported by Carreira.

D. F. Taber, Org. Chem. Highlights 2023, November 6.