One of the more specific goals of our research group has been to uncover useful synthetic methodology related to the chemistry of vinamidinium salts and their derivatives. One important class of compounds for which vinamidinium salts might serve as precursors are pyrroles and related compounds. The synthesis of pyrrole derivatives has been actively pursued in recent years due in part to the pharmacological properties of certain members of this class of substances. The goal of the organic synthesis described herein will be to establish and understand the use of vinamidinium salts and related compounds as efficient and useful reagents for the preparation of functionalized pyrroles. We propose a three phase study of the reaction of alpha-amino acid esters and related compounds with vinamidinium salts. Phase one will involve looking at substituent effects of the reactants in the condensation process. Phase two will deal with analogous reactions with unsymmetrical salts (vinamidinium and chloropropeniminium). Phase three will involve the generation of disubstituted chloropropeniminium salts and their conversion to regioselectively functionalized trisubstituted pyrroles. The overall study should define and delineate this methodology for the preparation of functionalized pyrroles.
