Progress Toward the Synthesis of Apomorphine: Chiral Auxiliary Mediated Interception of an Intramolecularly Formed N-Acyl Iminium Ion

Abstract

Glaucine, which contains an aporphine skeleton, has been previously synthesized utilizing an intermolecular approach to form an iminium ion for the Pictet-Spengler reaction. A diastereomeric excess of 79% resulted as mediated by a chiral auxiliary. Progress was made in attempting to increase the diastereomeric excess by using an intramolecular approach to iminium ion formation. Apomorphine is a suitable platform on which to demonstrate the asymmetric interception of a chiral N-acyl iminium ion generated by intramolecular means.

Several routes to this end were explored. These routes included the use of an intramolecular variant on the previously published work, Grubbs' metathesis and Horner-Wadsworth-Emmons among others. While no route proved successful in the end, understanding of the formation of aporphine skeletons was expanded upon.