Kinetic Resolution of Cyclic Enol Ethers by Pd-Catalyzed [1,3] O-C Rearrangement

Abstract

This thesis concerns the development of kinetic resolution of cyclic enol ethers utilizing a Pd-catalyzed [1,3] O-C rearrangement reaction. The required enol ethers were prepared from commercially available starting materials in good to excellent yields. The Pd-catalyzed [1,3] O-C rearrangement of these enol ethers in the presence of a chiral ligand proceeds smoothly via a kinetic resolution process returning remaining starting material with low to excellent levels of enantioselectivity. Enantiomerically enriched enol ethers were further transformed to a series of carbo- and heterocyclic products in good yield and with excellent levels of stereocontrol. Synthesis of (R)-goniothalamin was successfully accomplished via stereoselective transformations from an enantioenriched enol ether starting material. Aspects of the reaction mechanism are described, which resulted in the development of a model that explains the observed selectivities in the kinetic resolution. DFT studies aimed at providing a better understanding of the underpinning reasons for these selectivities are also described.