Organic Chemistry Portal
Organic Chemistry Highlights

Monday, April 21, 2008
Douglass F. Taber
University of Delaware

Synthesis of Dysiherbaine (Hatakeyama), Jerangolid D (Markó) and (+)-Spirolaxine Me Ether (Trost)

Several new developments in enantioselective C-O ring construction have been applied in the syntheses of natural products. To achieve control, the oxygenated quaternary center of dysiherbaine (9) must be established under kinetic conditions. One approach would be SN2 opening, but this would require displacement at a fully-substituted center. Susumi Hatakeyama of Nagasaki University has shown (Chem. Commun. 2007, 4158. DOI: 10.1039/b709627e) that the epoxide 6, prepared by the Sharpless procedure, undergoes just such an opening under mild acid catalysis.

Another approach to highly-substituted tetrahydrofurans and tetrahydropyrans is to join two carbons of a preformed chiral ether, such as 18. This is the strategy that István E. Markó employed in his recent (J. Am. Chem. Soc. 2007, 129, 3516. DOI: 10.1021/ja0691728) synthesis of jerangolid D (22). The key step was the three-component coupling of 15, 16, and 17, using a protocol recently developed in his group. Again using a procedure his group had developed, the trisubstituted alkene of 21 was prepared by modified Julia coupling of the ketone 19 with the anion of sulfone 20, followed be esterification and reduction.

The spiroketal (+)-spiroxaline methyl ether (32) contains three secondary oxygenated stereogenic centers. In a showcase of current chiral technology, Barry M. Trost of Stanford University constructed (Angew. Chem. Int. Ed. 2007, 46, 7664. DOI: 10.1002/anie.200702637) the first two of the three alcohols by the enantioselective addition of an alkyne to an aldehyde. The chiral catalyst 25 that directed the alkyne additions was derived from a commercial ligand. The last alcohol center was derived from R-(+)-epoxypropane. Note that the spiroketal was not prepared in the usual way, by acid-catalyzed cyclization of a dihydroxy ketone, but by Pd-catalyzed cyclization of the alkyne diol 31.

D. F. Taber, Org. Chem. Highlights 2008, April 21.