The intramolecular nitrile oxide cycloaddition (INOC) route to the ergot alkaloids: Use of the isoxazoline to γ-amino alcohol conversion in the total synthesis of (+)-paliclavine

Abstract

A total synthesis of the ergot alkaloid paliclavine ( 20 ), in optically active form is described. The synthesis scheme is based on the intramolecular dipolar cycloaddition reaction of a nitrile oxide to a neighboring olefinic appendage bearing an allylic asymmetric center. The extent of diastereofacial selection in the intramolecular nitrile oxide cycloaddition (INOC) reaction was found to be marginal. A single-crystal X-ray analysis has established the complete stereostructure of the isoxazoline 15 prepared from the “major” INOC product. The dependence of the reduction stereochemistry of the isoxazolinium salt 15a on the nature of the reducing agent is discussed.