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.

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. The final acid-catalyzed spiroacetalization provided the desired spiroacetal 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 assigned unambiguously through NMR spectroscopic studies.

Convergent Access to Bis-Spiroacetals Through a Sila-Stetter-KetalizationCascade. -The NHC-catalyzed title reaction between aliphatic acylsilanes and vinylketones bearing silyl ether groups affords bis-spiroacetals (IV) and (XV) in two steps. The two-step sequence carried out in a one-pot manner leads to the desired products in high yields [e.g. (IV)]. The reaction of compound (IIIb) with MeOH affords bis-acetal (VI). The selective formation of tetrahydrofurans is also possible [e.g. reaction of (IX)]. -(LABARRE-LAINE, J.; BENIAZZA, R.; DESVERGNES, V.; LANDAIS*, Y.; Org. Lett. 15 (2013) 18, 4706-4709, http://dx.doi.org/10.1021/ol402017x ; Inst. Sci. Mol., Univ. Bordeaux, F-33405 Talence, Fr.; Eng.) -C. Gebhardt 04-094