Synthesis of Indoles via Intermolecular and Intramolecular Cyclization by Using Palladium-Based Catalysts

Umer Rashid,Nasir Rasool,Imtiaz Ali,Muhammad Bilal,Samreen Gul Khan,Humaira Altaf,Ayesha Ayesha

doi:10.3390/catal11091018

Abstract

As part of natural products or biologically active compounds, the synthesis of nitrogen-containing heterocycles is becoming incredibly valuable. Palladium is a transition metal that is widely utilized as a catalyst to facilitate carbon-carbon and carbon-heteroatom coupling; it is used in the synthesis of various heterocycles. This review includes the twelve years of successful indole synthesis using various palladium catalysts to establish carbon-carbon or carbon-nitrogen coupling, as well as the conditions that have been optimized.

Highlights

Baeyer and Kop discovered indole in 1866 while researching a plant named indigo, which is known as benzopyrrole
Indoles are important heterocyclic compounds because they are an integral part of many alkaloids and biologically active compounds [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20]
In 2010, Ototake and coworkers stated that the reaction utilizing basic reagents or transition-metal catalysts has been reported as an effective method for constructing indole nuclei [107,127,128,129,130]

Summary

Introduction

In 2010, Ototake and coworkers stated that the reaction utilizing basic reagents or transition-metal catalysts has been reported as an effective method for constructing indole nuclei [107,127,128,129,130] They firstly synthesized optically active atropisomeric compounds, N-(o-tert-butyl phenyl)indole derivatives (5) by palladium-catalyzed asymmetric 5-endo-hydroamino cyclization of the achiral N-(o-tert-butylphenyl)-2-alkynylanilines (4), affording approximately 83% (ee) product (Scheme 3) [131]. In 2014, Yamaguchi and Manabe synthesized 4-Chloroindoles (33) by reacting derivatives of 2,3-dichloroaniline (31) with terminal alkynes (32) using a catalyst made up of palladium and dicyclohexyl-(dihydroxy terphenyl)phosphine (Cy-DHTP)(L2) (Scheme 12) This catalyst carried out the reaction selectively at the ortho-position involving Sonogashira cross-coupling followed by subsequent cyclization to produce 4-chloroindoles providing high yields.

50 COCNFH3

F NO2 n-Bu

75 Ph R1Ph

34 Ro3f1880of 85 N H

PdOAc NR 304

Indole Synthesis via Hydroamination or N-Arylation

Findings

H R1 N R2