Synthesis of the C10-C24-bis-spiroacetal core of 13-desmethyl spirolide C based on a sila-Stetter-acetalization process.

Synthesis of the bis-spiroacetal core of 13-desmethyl spirolide C has been completed based on a sila-Stetter-acetalization process. The acylsilane and enone partners in the Stetter reaction were prepared in 7 and 11 steps, respectively, from (S) and (R)-aspartic acid. The quaternary center at C19 in the enone moiety was controlled by relying on the Seebach's chiral self-reproduction method using an enantiopure (S)-lactic acid based dioxolanone.

Convergent access to bis-spiroacetals through a Sila-Stetter-ketalization cascade.

An NHC-catalyzed sila-Stetter reaction between aliphatic acylsilanes and vinylketones bearing silyl ether substituents affords functionalized 1,4-diketones, which upon treatment under acidic conditions leads to the corresponding bis-spiroacetals. The two-step sequence may also be carried out in a one-pot operation leading to high yields of the desired bis-spiroacetals.