Recent approaches in the organocatalytic synthesis of pyrroles (original) (raw)

A Critical Review on Advances in the Multicomponent Synthesis of Pyrroles

Oriental Journal of Chemistry, 2018

Nitrogen containing heterocyclic compounds are biologically significant molecules. This is especially true for pyrrole a five membered nitrogen containing aromatic molecule, which is present as a key structural motif in a large number of drugs and lead molecules. This review aims to provide an overview of the multi-component reaction (MCR) based methodologies used for the synthesis of pyrrole and its derivatives, focusing particularly on eco-friendly methods that avoid the use of hazardous reagents, solvents and catalysts are deemed especially relevant to the disciplines of medicinal chemistry and drug discovery.

Synthesis of Pyrrole and Substituted Pyrroles (Review)

2018

Pyrrole is widely known as a biologically active scaffold which possesses a diverse nature of activities. The combination of different pharmacophores in a pyrrole ring system has led to the formation of more active compounds. Pyrrole containing analogs are considered as a potential source of biologically active compounds that contains a significant set of advantageous properties and can be found in many natural products. The present review highlights the synthetic methods of representatives of nitrogen heterocycles such as pyrrole, substituted pyrroles and other related compounds. The aim of this review is to indicate and summarise the different methods for the synthesis of nitrogen containing heterocycles from the group of pyrrole and pyrrole related structures.

Paal–Knorr synthesis of pyrroles: from conventional to green synthesis

Catalysis Reviews, 2018

The pyrrole molecular framework is found in a large number of natural and synthetic compounds of great importance. Since functionalized pyrroles are essential for the progress of many branches of science, its synthesis by simple, efficient and ecofriendly routes are particularly attractive in modern organic and bio-organic chemistry. To this end, a number of synthetic methods have been developed, in which the Paal-Knorr pyrrole synthesis stands out to be the easiest route to synthesize pyrroles. In spite of the efficiency, Paal-Knorr synthesis of pyrroles is considered limited by harsh reaction conditions, such as prolonged heating in acid, which may degrade sensitive functionalities in many potential precursors. Through this route almost all dicarbonyls can be converted to their corresponding heterocycles and therefore it is a synthetically valued process. To address the adverse issues this reaction route has undergone numerous modifications recently and today it can be said that this reaction route is a prominent green route for the synthesis of pyrroles. This review is a tour from the evolution and application of this harsh synthetic route to the ecofriendly greener route developed for the synthesis of pyrroles.

Fast, Efficient, Mild, and Metal-Free Synthesis of Pyrroles by Domino Reactions in Water

Organic Letters, 2010

(E)-Bromonitrostyrenes react with enaminones in water to afford pyrroles in excellent yields. The domino reaction constitutes a new, mild, and environmentally benign process for the fast and efficient synthesis of diverse pyrroles. Among the many heteroaromatic compounds, the pyrrole ring has found a wide number of applications and is present in many natural products. 1 It is used as an important skeleton in organic synthesis 2 and is also utilized in other important fields, such as materials science, 3 medicinal chemistry, and pharmacology. 4 Therefore, a large effort has been made to develop more efficient synthetic routes to obtain this valuable heterocycle. 5 The most frequently used methods are the classic Hantzsch, 6 Knorr, 7 and Paal-Knorr 8 procedures. Although these methods have been used during the last century, there are significant drawbacks which have triggered the search for new methodologies, such as multicomponent couplings 9 and transition-metal-catalyzed cyclizations. 10 The success of these newer methods is often limited as in many

Merging Gold and Organocatalysis: A Facile Asymmetric Synthesis of Annulated Pyrroles

Chemistry - A European Journal, 2014

The combination of cinchona-alkaloid-derived primary amine and Au I-phosphine catalysts allowed the selective C-H functionalization of two adjacent carbon atoms of pyrroles under mild reaction conditions. This sequential dual activation provides seven-membered-ring-annulated pyrrole derivatives in excellent yields and enantioselectivities. Keywords annulation; gold catalysis; organocatalysis; primary-amine catalysis; pyrroles Although gold catalysis and organocatalysis have rapidly grown since the turn of the millennium and emerged as powerful tools in the general field of catalysis, examples of the combination of gold and organocatalysis in sequential and cooperative tandem reactions exploiting complementary activation modes are still scarce. [1-3] Recently, we reported the asymmetric synthesis of tetracyclic indole derivatives containing seven-membered rings by the merger of a thioamide-based organocatalyst with a Au I catalyst to effect two consecutive Friedel-Crafts-type reactions on unsubstituted indole substrates (Scheme 1a). [4] Due to the immense importance of the indole core, major emphasis has been given to the development of asymmetric Friedel-Crafts reactions involving indole derivatives. Pyrrole is another electron-rich heteroaromatic compound, core of which is found in many natural products. [5,6] One attractive aspect of pyrrole chemistry that is unseen in indole substrates is the inherent nucleophilicity on the C2 position, which stands in contrast to indoles having a classical C3 nucleophilic site. Because Michael-type reactions of pyrroles usually gives 2,5dialkylated products, it is difficult to monofunctionalize pyrrole substrates (Scheme 1c). [7] To avoid this problem, we wanted to selectively functionalize two adjacent sites on the pyrrolic heterocycle by using two different catalytic modes of activation to generate new

One-Pot Four-Component Synthesis of Tetrasubstituted Pyrroles

Helvetica Chimica Acta, 2008

A convenient one-pot four-component synthesis of tetrasubstituted pyrroles was carried out through the reaction of butane-2,3-dione with a-aminophosphorous ylides, obtained in situ from the 1 : 1 : 1 addition reaction between triphenylphosphine, dialkyl acetylenedicarboxylate, and ammonium acetate.