N-Acyl pyrroles: chemoselective pyrrole dance vs. C–H functionalization/aroylation of toluenes

Abstract

Chemoselectivity is one of the most challenging issues facing the chemical sciences. In this study, the first highly chemoselective reactions of N-acylpyrroles via either an anionic Fries rearrangement (pyrrole dance) or a C–H functionalization of toluene to provide aryl benzyl ketones are advanced. This efficient and operationally simple approach enables the synthesis of either 2-aroylpyrroles or aryl benzyl ketones in good to excellent yields under transition metal-free conditions. The choice of base plays a crucial role in controlling the chemoselectivity. The aroylation of toluene derivatives was observed with N-acylpyrroles when subjected to KN(SiMe₃)₂, while anionic Fries rearrangement products were produced with LiN(SiMe₃)₂. Surprisingly, cross-over experiments indicate that the anionic Fries rearrangement is an intermolecular process. The aroylation reaction has the advantage over Weinreb amide chemistry in that it does not require preformed organometallic reagents or cryogenic temperatures.