Preparation of a Spiroacetal Subunit by Using an Asymmetric Aldol Reaction

Significance

A solid-phase methodology for the stereoselective synthesis of highly substituted spiroacetals was developed and applied to the preparation of an AB-spiroacetal subunit 1 (5% yield, over 9 steps). The key steps in this approach were the asymmetric boron-mediated aldol reactions on solid support. The solid-supported aldehyde 3 reacted with a chiral boron enolate of acetone to give the supported aldol 4. The solid-supported boron enolate 5 derived from aldol 4 reacted with aldehyde 6 to give 7 from which the spiroacetal 1 was readily released via acidic cleavage.