Asymmetric synthesis of andavadoic acid via base-catalyzed 5-exo-tet cyclization of a β-hydroperoxy epoxide

The first total synthesis of andavadoic acid, a naturally occurring five-membered ring peroxide, and its absolute configuration assignment are reported. Central to this venture was the development of an effective synthesis of a key beta-hydroperoxy epoxy ester from (R)-epichlorohydrin via chemoselective methylenation with Nysted reagent in the presence of Ti(Oi-Pr)(2)Cl-2 and chemo- and regioselective Mukaiyama-Isayama peroxidation. This approach also featured the construction of the 1,2-dioxolane ring system by an efficient base-promoted 5-exo epoxide opening by a hydroperoxy group. (C) 2012 Elsevier Ltd. All rights reserved.