An interrupted Heyns rearrangement approach for the regioselective synthesis of acylindoles

An efficient and general method for the synthesis of 2- and 3-acylindoles has been achieved with high regioselectivity from o-acylanilines and α-hydroxycarbonyl or its equivalent. The strategy involves the intramolecular trapping of an in situ generated aminoenol intermediate and an interrupted Heyns rearrangement pathway, followed by aromatization or rearrangement/aromatization. Important features include excellent regiocontrol, good functional group tolerance, operational simplicity and application to gram-scale synthesis and the synthesis of an anti-tumor agent.