Synthetic Strategies Toward Tetrahydrofurans Involving Double Diastereoselective Nucleophile-Promoted Aldol-Lactonizations and Subsequent Applications to Bioactive Natural Products

Abstract

Novel synthetic strategies towards the formation of tetrahydrofurans and their subsequent application to bioactive natural products have been explored. More specifically, a method for invoking double-diastereoselectivity in the formation of tetrahydrofuran-fused β-lactones through nucleophile-catalyzed aldol-lactonization (NCAL) has been developed. By employing a chiral catalyst, such as OTMS-quinidine or OTMS-quinine, coupled with a chiral aldehyde acid substrate, we have been able to successfully override the inherent substrate stereochemical bias to access either diastereomeric product as the major adduct. This new methodology is being applied to construction of the tetrahydrofuran fragment of the cytotoxic agent, haterumalide NA.