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Organic Chemistry Highlights

Total Synthesis

Monday, January 1, 2007
Douglass Taber
University of Delaware

Synthesis of (-)-Colombiasin A and (-)-Elisapterosin B

Historically, there have been three methods for assembling enantiomerically-pure carbocycles: cyclization of an enantiomerically-pure starting material, enantioselective cyclization of a prochiral substrate, and enantioselective transformation of a prochiral cyclic starting material. Recently, a fourth strategy has been developed, enantioselective transformation of a racemic starting material, with only one enantiomer of the starting material going on to the desired product. This approach is illustrated by the transformation of racemic 1 to enantiomerically (and diastereomerically) pure 3. The conversion of 1 to 3 is the key step in a general route established (J. Am. Chem. Soc. 2006, 128, 2485. DOI: 10.1021/ja056877l) by Huw M. L. Davies of the University at Buffalo to the diterpenes isolated from the gorgonian coral Pseudoterogoria elisabethae, exemplified by (-)-colombiasin A (4).

The dihydronaphthalene 1 was prepared by Diels-Alder cycloaddition of the diene 5 to the benzoquinone 6, the preparation of which had been reported by Nicolaou in the course of a previous synthesis of (-)-colombiasin A (4). Silylation of the cycloadduct followed by selective hydrolysis gave the ketone 7. The ketone was converted to the enol triflate 8, which was reduced with triethylsilane to give racemic 1.

Exposure of 1 to 2 in the presence of the DOSP Rh catalyst, designed by Davies, delivered the two adducts 8 and 9. These were carried together to the alcohols 10 and 11, which were separated. The overall yield of diasteromerically- and enantiomerically-pure 11 from racemic 1 was 34%. This was 68% of theoretical, since was derived from only one of the two enantiomers of 1.

Homologation of 11 to the diene followed by desilylation under oxidative conditions led to the quinone 12. Followed the precedent of Rychnovsky, on heating 12 was converted to the Diels-Alder adduct 13. Demethylation then gave (-)-colombiasin A (4).

The tetracyclic triketone (-)-elisapterosin B (14), also a Pseudoterogoria elisabethae diterpene, is the intramolecular [5 + 2] cycloaddition product from 12. Again following a Rychnovsky procedure, exposure of the diene 12 to BF3 etherate led directly to 14, accompanied by minor amounts of the methyl ether 13.

D. F. Taber, Org. Chem. Highlights 2007, January 1.