A Highly Selective Indoxyl‐Free Synthesis of Indirubins From Isatins and 2‐Aminoacetophenones via a Knoevenagel Condensation–Cyclization Cascade

A base‐mediated condensation of isatins with readily accessible 2‐aminoacetophenones or 2‐aminophenacyl bromides for the synthesis of indirubins has been realized. In contrast to most reported methods, which proceed through an “indoxyl” intermediate and often generate indigo as a side product via self‐dimerization, the present protocol selectively affords ( Z )‐indirubins, owing to a distinct substrate‐specific mechanistic pathway. The method features broad substrate scope, avoids chromatographic purification, and employs commercially available isatins and synthetically accessible 2‐aminoacetophenones or 2‐aminophenacyl bromides as starting materials, highlighting its practical applicability and synthetic utility.