Synthesis of Racemic g-Azido-a,b-Unsaturated Nitrile.

Abstract

For years pharmaceutical companies have struggled with the side effects caused by racemic mixtures of pharmaceutical drugs because all biological systems are based on asymmetric processes.It is important to develop a synthetic scheme that produces one drug enantiomer over the other.The overarching goal of this research is the development of synthetic methodologies that permit facile, enantiocontrolled access to molecules of biological importance.More specifically, these studies are directed toward the synthesis of enantiomerically enriched (R)-g-azido-a,b-unsaturated nitrile.These highly functionalized products offer great versatility as chiral building blocks for the preparation of enantioenriched pharmaceutical compounds.The product, (R)-g-azido-a,b-unsaturated nitrile, is synthesized in a three-step sequence that unites the enantioselectivity of an enzyme with the rich chemistry of palladium.First a stereocenter is induced into an achiral a,b-unsaturated aldehyde which is then easily be converted into its corresponding carbonate.The third reaction involves the replacement of the carbonate with an azide via a 1,3 palladium-catalyzed transfer.A one step method for producing the cyanohydrin carbonate allowed a large-scale racemic production of this molecule.This increased the availability of the substrate and allowed for optimization of a reaction conditions for the palladium reaction.