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Organic Chemistry Highlights

Total Synthesis

Monday, March 1, 2021
Douglass F. Taber
University of Delaware

The Wang Synthesis of 11-O-debenzoyltashironin

11-O-Debenzoyltashironin (3), isolated from Illicium merrillianum, an evergreen shrub of East Asia, showed powerful neurotrophic activity. Bo Wang of Jilin University envisioned assembling the trans-fused 6/5 ring system of 3 by the Pd-catalyzed cyclization of 1 to 2 (Org. Lett. 2020, 22, 2730. DOI: 10.1021/acs.orglett.0c00689).

The synthesis began with the Diels-Alder cycloaddition of commercial 2,3-dimethyl maleic anhydride (4) with Danishefsky's diene (5). Hydrolysis of the product enol ether led to the ketone 6. Selective methoxide opening of the anhydride followed by reduction and reoxidation delivered the lactone 7. Nucleophilic epoxidation of the enone followed by acetoxylation gave 8. Addition of the Grignard reagent 9 followed by deactylation and oxidation led to 10. The ketone 12 was prepared by addition of the propargyl zinc reagent 11 followed by base treatment to rearrange the epoxide and Dess-Martin oxidation. Acetylation, elimination of the epoxide and silylation then completed the assembly of the ene yne 1.

The cyclization of 1 probably proceeded by initial complexation of the Pd catalyst with the alkyne, leading to 13. Nucleophilic addition of the enol ether with concomitant debenzylation would then give the aldehyde 2.

The two carbonyls of 2 were in close enough proximity that exposure of 2 to excess Ti(III) led to cyclization to 14. Hydrolysis exposed the ketone 15, that was hydrogenated to 16. Removal of the extraneous -OH by reduction with Sm(II) then completed the synthesis of racemic 11-O-debenzoyltashironin (3).

D. F. Taber, Org. Chem. Highlights 2021, March 1.