Dihydroxy spiroketals

Dihydroxy spiroketals are available based on a protocol by Ding et ed. [45] by base-assisted condensation of HO-protected benzaldehyde derivatives with cyclic ketones, followed by hydrogenation of the olefins and final cleavage of the methylether groups with BBrj (Scheme 2.74). 

Scheme 2.74 Synthesis of dihydroxy spiroketals. seven steps...

Spiroacetals (spiroketals). A widely distributed class of natural products with characteristic structural features intramolecular ring closure of a dihydroxy ketone furnishes a bicycUc compound in which one carbon atom (that of the original carbonyl group) is shared by both rings. This so-called spiro center is bound to one carbon atom and one oxygen atom in both rings. 

Most examples of spiroketaHzation involve an acid-catalyzed dehydration of dihydroxy ketones. However, the required acidic conditions are not always compatible with the presence of labile functional groups. Consequently, metal-catalyzed spiroketaHzations have been developed and a wide variety of metal complexes [Au(I), Au(III), Pd(II), Hg(II), Ir(I), Rh(I), Pt(II)] can be used to access spiroketals (2012S3699). 

The spiroketal (+)-spiroxaliiie methyl ether 31 contains three secondary oxygenated ste-reogenic centers. In a showcase of current chiral technology, Barry M. Trost of Stanford University constructed (Angew. Chetn. Int. Ed. 2007, 46, 7664) the first two of the three alcohols by the enantioselective addition of an aUsyne to an aldehyde. The chiral catalyst 25 that directed the alkyne additions was derived from a commercial Hgand. The last alcohol center was derived from / -(+)-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 30. 

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