Lithium-Promoted Cycloaddition of Indole-2,3-dienolates and Carbon Disulfide as a One-Pot Route to Thiopyrano[4,3-b]indole-3(5H)-thiones

Abstract

A new approach for the annulation of a thiopyrane ring to an indole core under mild conditions was developed. Treating 2-methyl-3-acylindoles with lithium diisopropyl amide leads to the elimination of a proton from the 2-methyl group. The lithium indole-2,3-dienolates obtained were found to react with CS2 to give the corresponding thiopyrano­[4,3-b]­indole-3­(5H)-thiones. The mechanism represents a stepwise addition through ion-pair formation, according to PCM/B3LYP/6-311++G**, PBE1PBE/6-311++G**, and MP2//HF/6-311++G** quantum chemical calculations. AIM calculations revealed the essential role of the Li atom at all stages of the process.

Update on thiopyran-fused heterocycle synthesis (2013–2024)

“…Target compounds were prepared through an organocatalytic asymmetric cascade reaction based on their earlier More recently, in 2021, Vyalyh and co-workers reported the reaction of lithium indole-2,3-dienolates with carbon disulfide, which led to the synthesis of thiopyrano [4,3-b]indole-3(5H)thione of type 81 (Scheme 13). 31 The required lithium indole-2,3-dienolate 78 was generated from 2-methyl-3-acylindole 77 using lithium diisopropyl amide (LDA) by the elimination of a proton from the 2-methyl group. Initially, 2-methylindole 75 under Vilsmeier conditions was acylated to form 3-acyl-2methylindole 76, which was then alkylated to synthesize starting material 77.…”

DDQ/Fe(NO3)3-Catalyzed Aerobic Synthesis of 3-Acyl Indoles and an In Silico Study for the Binding Affinity of N-Tosyl-3-acyl Indoles toward RdRp against SARS-CoV-2

“…Providing more emphasis, indoles and their 3-substituted derivatives are always in the center of research because of their widespread applications in pharmaceuticals as potential drug candidates and in the discovery and development of novel functional materials. , In particular, synthesis of 3-acyl indoles has drawn the immense attention of organic synthetic chemists because of their relevance in natural products and pharmaceutical entities and their capability of binding with many biological receptors to show potential anti-tumor, antiviral, and anti-carcinogenic activity (Figure ), and so forth . Moreover, these 3-acylated indoles are versatile key intermediates involved in various functional group transformations to afford valuable simple to complex organic heterocyclic scaffolds. , Therefore, the synthesis of 3-acyl indoles is still of great interest and in the foci of research.…”