Recent Progress in the Transition Metal Catalyzed Synthesis of Indoles

Abstract

Indole is the most frequently found heterocyclic core structures in pharmaceuticals, natural products, agrochemicals, dyes and fragrances. For about 150 years, chemists were absorbed in finding new and easier synthetic strategies to build this nucleus. Many books and reviews have been written, but the number of new syntheses that appear in the literature, make necessary continuous updates. This reviews aims to give a comprehensive overview on indole synthesis catalyzed by transition metals appeared in the literature in the years 2016 and 2017.

Ultrathin Amorphous/Crystalline Heterophase Rh and Rh Alloy Nanosheets as Tandem Catalysts for Direct Indole Synthesis

“…Importantly, Rh‐based catalysts are among the most active catalysts for the indoles synthesis. [ 7–9 ] Particularly, heterogeneous Rh‐based catalysts are promising candidates owing to their stability, recyclability, and facile segregation. [ 10,11 ] However, they still suffer from the low catalytic activity and selectivity compared to the homogeneous catalysts.…”

Metal-Promoted Heterocyclization: A Heterosynthetic Approach to Face a Pandemic Crisis

“…Indole is one of the most common heterocyclic scaffolds, used in a large array of drugs, natural products, and agrochemicals. The importance of this aromatic N -heterocycle has been highlighted by the continuous work carried out on it [ 66 ]. In this section, we suggest some recent metal-catalyzed heterocyclization pathways to achieve polysubstituted indoles in an easy and accessible way with the aim of finding plausible alternative strategies for the synthesis of the indole core present in Arbidol.…”

One-pot, three-component Fischer indolisation–N-alkylation for rapid synthesis of 1,2,3-trisubstituted indoles

“…[10][11][12] Accordingly, indole synthesis has a long and distinguished history, and the many published protocols for generating and elaborating the indole core ensure that few indole structures are beyond the reach of the present-day synthetic chemist. [13][14][15][16][17] Our recent studies into structurally-diverse spiropyrans 4,18 required a broad range of 1,2,3-trisubstituted indole building blocks and, to meet this demand, we have developed a rapid, cheap and concise one-pot, three-component sequence for their synthesis, based upon Fischer indolisation-N-alkylation, and the evolution of this process is described herein. 19 One-pot, multistep regimens can provide efficiency in terms of time, cost, yield, labour, energy and consumables, [20][21][22] and the combination of Fischer indole synthesis and indole N-alkylation is inherently geared towards successful application as a rapid one-pot process for two principal reasons: (i) Fischer indolisation and indole N-alkylation are robust, clean, high-yielding processes which generate minimal quantities of by-products or leftovers, hence are ideal within one-pot, multicomponent reaction cascades; (ii) indole N-alkylation is rapid (commonly < 1 hour) and whilst Fischer indolisation displays more varied reaction rate, use of microwave irradiation often leads to short reaction times (<10 minutes).…”