Singh Chauhan Amar Nath, Mali Ghanshyam, Dua Garima, Samant Priya, Kumar Akhilesh, Erande Rohan D
Department of Chemistry, Indian Institute of Technology Jodhpur, Jodhpur 342037, India.
Department of Chemistry and Nano Science, Ewha Womans University, Seoul 03760, Korea.
ACS Omega. 2023 Jul 25;8(31):27894-27919. doi: 10.1021/acsomega.3c02510. eCollection 2023 Aug 8.
Polycyclic fused indoles are ubiquitous in natural products and pharmaceuticals due to their immense structural diversity and biological inference, making them suitable for charting broader chemical space. Indole-based polycycles continue to be fascinating as well as challenging targets for synthetic fabrication because of their characteristic structural frameworks possessing biologically intriguing compounds of both natural and synthetic origin. As a result, an assortment of new chemical processes and catalytic routes has been established to provide unified access to these skeletons in a very efficient and selective manner. Transition-metal-catalyzed processes, in particular from rhodium(III), are widely used in synthetic endeavors to increase molecular complexity efficiently. In recent years, this has resulted in significant progress in reaching molecular scaffolds with enormous biological activity based on core indole skeletons. Additionally, Rh(III)-catalyzed direct C-H functionalization and benzannulation protocols of indole moieties were one of the most alluring synthetic techniques to generate indole-fused polycyclic molecules efficiently. This review sheds light on recent developments toward synthesizing fused indoles by cascade annulation methods using Rh(III)-[RhCp*Cl]-catalyzed pathways, which align with the comprehensive and sophisticated developments in the field of Rh(III)-catalyzed indole functionalization. Here, we looked at a few intriguing cascade-based synthetic designs catalyzed by Rh(III) that produced elaborate frameworks inspired by indole bioactivity. The review also strongly emphasizes mechanistic insights for reaching 1-2, 2-3, and 3-4-fused indole systems, focusing on Rh(III)-catalyzed routes. With an emphasis on synthetic efficiency and product diversity, synthetic methods of chosen polycyclic carbocycles and heterocycles with at least three fused, bridged, or spiro cages are reviewed. The newly created synthesis concepts or toolkits for accessing diazepine, indol-ones, carbazoles, and benzo-indoles, as well as illustrative privileged synthetic techniques, are included in the featured collection.
多环稠合吲哚因其巨大的结构多样性和生物学意义而广泛存在于天然产物和药物中，这使得它们适合探索更广阔的化学空间。基于吲哚的多环化合物因其独特的结构框架包含天然和合成来源的具有生物学吸引力的化合物，仍然是合成制备中既引人入胜又具有挑战性的目标。因此，已经建立了一系列新的化学过程和催化路线，以非常高效和选择性的方式统一获得这些骨架。过渡金属催化的过程，特别是铑（III）催化的过程，被广泛用于合成努力中以有效地增加分子复杂性。近年来，这在基于核心吲哚骨架获得具有巨大生物活性的分子支架方面取得了重大进展。此外，铑（III）催化的吲哚部分的直接C-H官能化和苯并环化方案是高效生成吲哚稠合多环分子的最具吸引力的合成技术之一。本综述阐述了使用铑（III）-[RhCp*Cl]催化途径通过级联环化方法合成稠合吲哚的最新进展，这与铑（III）催化的吲哚官能化领域的全面和复杂发展相一致。在这里，我们研究了一些由铑（III）催化的有趣的基于级联的合成设计，这些设计产生了受吲哚生物活性启发的精细框架。该综述还强烈强调了获得1-2、2-3和3-4稠合吲哚体系的机理见解，重点是铑（III）催化的路线。强调合成效率和产物多样性，对具有至少三个稠合、桥连或螺环的选定多环碳环和杂环的合成方法进行了综述。特色集合中包括用于获得二氮杂卓、吲哚酮、咔唑和苯并吲哚的新创建的合成概念或工具包，以及示例性的特权合成技术。
