High yielding allylation of a chiral secondary alcohol containing base sensitive functional groups

Abstract

Inhibitors of neuronal nitric oxide synthase, based on a chiral pyrrolidine scaffold, show promise for the treatment of certain neurodegenerative diseases. We recently reported the synthesis of a series of selective inhibitors, but the method was limited at a key step of forming an allyl ether intermediate. Yields for this step were very inconsistent, and the presence of base sensitive functional groups limited the range of available methods for forming this ether bond. This work describes a novel application of palladium catalyzed decarboxylative allylation, consistently resulting in a 90% isolated yield, which is crucial for the synthesis of this critical late stage intermediate. We also report a new quantitative yielding and straightforward synthesis of the allyl-t-butylcarbonate precursor.