Acylative Coupling of Amine and Indole Using Chloroform as a Carbonyl Group

Abstract

Chloroform‐mediated acylative coupling of amines with indoles has been developed. When indoles and amines in chloroform were treated with dimethylzinc in the presence of air, the three‐component aminocarbonylation reaction proceeded via in‐situ generation of phosgene from chloroform and O2 to provide indole‐3‐carboxamides in a single operation. Application to the synthesis of biologically active compounds and intramolecular acylation are also described.

Recent Advances of Three‐component Reactions of Simple Indoles

“…Miyata et al [46a] . used chloroform (CHCl 3 ) as precursor of phosgene (COCl 2 ) via a radical mechanism.…”

1,4,2-Dioxazol-5-ones as Isocyanate Equivalents: Chemoselective Non-Metal-Catalyzed Carboxamidation of Indoles

“…7 8 (Scheme 1 ) An interesting method involves the acylative coupling of an indole and an amine by using chloroform as the source of the carbonyl group. 9 Although this method provides much-needed generality for the synthesis of diverse indole-3-carboxamides, it involves the use of dimethylzinc to generate phosgene, which could be hazardous on a large scale.…”

Exploiting Chloroform-COware Chemistry for Pd-Catalyzed Carbonylation of Naturally Occurring and Medicinally Relevant Phenols

“…In recent years, chloroform has gained recognition as a cost-effective and widely available CO source . Despite the exploration of one-pot chloroform-enabled reactions, their application is constrained by the need for a strong basic condition (6–10 equiv of KOH/CsOH·H 2 O) for hydrolysis of chloroform, potentially affecting the functional group tolerance of substrates.…”