Efficient Et3N‐Catalyzed three‐Component Synthesis of 4,5,6,7‐Tetrahydro‐3‐Cyanoindoles and its Conversion to 3‐Cyanoindoles

We report a highly efficient and scalable one‐pot Et₃N‐catalyzed cascade reaction for synthesizing 4,5,6,7‐tetrahydro‐3‐cyanoindoles from hydroxycyclohexanone dimers, oxoacetonitriles, and primary amines in up to 91 % yield. This reaction proceeds through aldol condensation, cyclization via Paal‐Knorr synthesis, and subsequent aromatization under mild, cyanide‐free and metal‐free conditions. The reaction uses readily available starting materials and accommodates a broad substrate scope, including diverse oxoacetonitriles and aliphatic or aromatic amines, without significant variations in yield. Gram‐scale synthesis demonstrates its practical applicability, producing the target compounds with consistent efficiency. Additionally, the 4,5,6,7‐tetrahydro‐3‐cyanoindoles were successfully converted to their corresponding 3‐cyanoindoles, emphasizing the synthetic versatility of this approach and offering a practical and more environmentally friendly alternative for generating these compounds.