A Domino One-Pot Approach to Functionalized Benzonitriles from 2-[(3-Hydroxy/acetoxy)propyn-1-yl]benzamides

Abstract

Functionalized benzonitriles, α,β-epoxyketones and β-hydroxy-α-haloketones are part of several medicinally important molecules. The benzonitriles possessing any of these functional groups may be of interest to medicinal chemists for further study. However, simultaneous incorporation of the nitrile group and these functional groups into the aromatic ring is a challenging task. Herein we report such an important strategy for the rapid and simultaneous construction of structurally novel benzonitrile derivatives, possessing either an ortho--iodo--hydroxyketones or an -epoxyketones or an -enone, from an unprotected, 2-[(3-hydroxy/acetoxy)-propyn-1-yl]benzamides. These benzonitriles are unique in their structural features and have been reported for the first time. This process involves NXS promoted dehydration¬–halohydration followed by DIPEA promoted either an epoxide formation (for alcohols). We have developed both stepwise as well as one-pot strategies to improve synthetic efficiency. No metal catalysts are employed in this process. These methods show good substrate scope and yields.