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Organic Chemistry Highlights

Total Synthesis

Monday, July 3, 2023
Douglass F. Taber
University of Delaware

The Carreira Synthesis of Aberrarone

The tetraketone aberrarone (3) was isolated from the feathery Caribbean gorgonian Pseudopterogorgia elisabethae. En route to 3, Erick M. Carreira of ETH Zürich devised the one-pot, two-step assembly of the pentacyclic aldol product 2 from the substituted cyclopentene 1 (J. Am. Chem Soc. 2022, 144, 15475. DOI: 10.1021/jacs.2c07150).

The cyclopentene 1 was assembled from three components, Roche ester 4, pantolactone (7), and 3-methylcyclopentenone (11). The Roche ester 4 was silylated, then reduced with Dibal to the aldehyde 5. Methoxymethylenation followed by hydrolysis converted 5 into the aldehyde 6.

Pantolactone (7) was protected, then reduced with Dibal and carried on to the alkene 8. Oxidation followed by the addition of the alkyne 9, desilylation and acetylation completed the assembly of the alkyne 10.

Following the Buchwald protocol, 3-methylcyclopentenone (11) was reduced to the bis-silyl enol ether 12. Generation of the enolate followed by the addition of the aldehyde 6 led to the alcohol as an inconsequential mixture of diastereomers, that were converted into their respective xanthates and reduced to the ketone 13. Conversion to the enol triflate 14 followed by coupling with the alkyne 10 led to 15, that was oxidized to the aldehyde 1.

The initial product from the gold-catalyzed rearrangement of 1 was the enol acetate 16. On combination with Bu3SnOCH3, this was converted to the tin enolate, that added to the aldehyde, leading to the pentacyclic 2.

Hydrogenation of the deprotected ketone led to cleavage of the wrong cyclopropane bond, so after deprotection the ketone was reduced to the alcohol. Hydrogenolysis then delivered the triol 17. Oxidation to the triketone followed by further oxidation with selenium dioxide completed the preparation of aberrarone (3).

D. F. Taber, Org. Chem. Highlights 2023, July 3.