Facile and rapid access to hexafluoroisopropanol (HFIP)-group-functionalized aniline and indole derivatives using hexafluoroacetone trihydrate in HFIP

Abstract

A series of structurally diverse HFIP-group-functionalized aniline and indole derivatives was prepared through a simple procedure using inexpensive and widely available hexafluoroacetone trihydrate in hexafluoroisopropanol (HFIP) at room temperature without any additional catalysts or additives. Notable features of this synthetic protocol include high efficiency, high atom economy, broad functional group tolerance, mild reaction conditions, low cost, as well as simple and practical operation, providing an attractive platform for large-scale, eco-friendly operations. The synthetic utility of this protocol was further demonstrated by the late-stage functionalization of biologically active molecules with potential pharmaceutical relevance and the application of such fluoroalcohol-based scaffolds as organocatalysts.