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-des- methyl spirolide C has been completed based on a sila-Stet- ter-acetalization process. The acylsilane and enone partners in the Stetter reaction were prepared in seven 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 by using an enantiopure (S)-lactic acid based dioxolanone. The final acid-catalyzed spiroacetalization provided the desired spiroa- cetal as a mixture of diastereoisomers in 13 linear steps. Whatever the conditions used, the non-natural transoid isomer was formed preferentially. However, both cisoid and transoid isomers were isolated pure and their structure as- signed unambiguously through NMR spectroscopic studies.