Intramolecular propargylic barbier reactions for the stereoselective synthesis of natural products.
Date of Issue2012
School of Physical and Mathematical Sciences
This thesis describes the implementation of the intramolecular Barbier reaction in the diastereoselective synthesis of butenolide natural products. The first chapter provides a brief overview of the intramolecular and intermolecular propargylic Barbier reaction together with regioselective and stereoselective challenges. The second chapter discusses a concise route to (-)-mintlactone starting from propargyl alcoholvia a highly diastereoselective intramolecular propargylicBarbier reaction. The third and fourth chapters describe the extension of this methodology to synthesize the Stemona alkaloids. The third chapter describes an efficient way to construct the seven-membered azepine ringin a synthesis of (±)-stemoamide starting from succinimide.The fourth chapter describes the construction of basic stenine ring system starting from pyrroleemploying an asymmetric organocatalyzed cyclization, Sonogashira coupling, a diastereoselectiveintramolecular propargylic Barbier reaction, and diastereoselectivealkene reduction. In addition, we also disclose a new strategy tocontrol the electron density of the pyrrole nucleus by using the trifluoromethyl ketone as anelectron withdrawing group.