Effect of C-9 Substituents on the Regioselectivity of A-Ring Reactions in Derivatives of the Wieland‒Miescher Ketone

Abstract

The nature of C-9 substituents Was found to have a significant influence on the regio- and stereochemistry of A-ring reactions in a variety of Wieland-Miescher ketone derivatives. For example, Pd-catalyzed hydrogenation of the C-9 dioxolanes resulted in much better selectivity for the cis-funded products vis-a-vis the corresponding C-9 ketone, with the parent Wieland-Miescher ketone itself and both C-4 methyl and C-4 carboalkoxy substituted analogues. In addition, methylation and acylation of A-ring enolates favored the C-2 isomer when a C-9 dioxolane group was present, but the C-4 substituted isomer was predominant with the corresponding C-9 ketone. These differences in regiochemistry may allow selective elaboration of cis-fused decalins during preparation of complex natural products.