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Post multicomponent reaction (MCR) transformations are one of the most successful methods leading to high structural diversity and molecular complexity. A well-known MCR, the Ugi reaction typically affords a linear peptide backbone, enabling post-Ugi transformations as an elegant solution to rigidify the Ugi adduct into more drug-like species. Not surprisingly, the development of such transformations leading to new structural frameworks has expanded rapidly over the last few years. These reactions have reached an impressive level of performance and versatility, particularly in amalgamation with gold catalysis. This review outlines the developments achieved in the past decade, highlighting the modifications that are performed in a sequential or domino fashion with emphasis on major concepts, synthetic applications of the derived products as well as mechanistic aspects., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A novel diversity-oriented access to (spiro)polyheterocycles possessing two adjacent quaternary carbon stereocenters is described. By combining an Ugi 4-CR with Pd-catalysis, the possible mode of cyclization is controlled by the appropriate choice of ligands. Using XantPhos, spirooxindoles are selectively generated, while with BINAP fused polycyclic cis-dihydrobenzofurans are obtained with high diastereoselectivity.

The Ugi-4CR is by far one of the most successful multicomponent reactions leading to high structural diversity and molecular complexity. However, the reaction mostly affords a linear peptide backbone, enabling post-Ugi transformations as the only solution to rigidify the Ugi-adduct into more drug like species. Not surprisingly, the development of these transformations, leading to new structural frameworks, has expanded rapidly over the last few years. As expected, palladium-catalyzed reactions have received the foremost attention, yet other metals, particularly gold complexes, are fast catching up. This tutorial review outlines the developments achieved in the past decade, highlighting the modifications that are performed in a sequential or domino fashion with emphasis on major concepts, synthetic applications of the derived products as well as mechanistic aspects.

The direct cross-coupling of tautomerizable heterocycles with various unfunctionalized heteroarenes has been achieved through PyBroP-mediated and Pd/Cu-catalyzed sequential C-OH/C-H activation. The methodology allows a facile entry into novel diazine-azole biheterocyclic frameworks. Moreover, an unprecedented Pd-catalyzed phosphonium homocoupling of tautomerizable heterocycles was also developed to afford a direct synthetic route to symmetrical 1,2-, 1,3-, and 1,4-bidiazine units.

The development of new strategies for synthesis of medium-sized heterocycles has remained a highly attractive but challenging proposition. In the last few years, the application of microwave irradiation has greatly facilitated the construction of such heterocyclic ring systems through a myriad of different synthetic approaches. This feature article illustrates the progress made in the microwave-assisted synthesis of medium-sized heterocycles with an emphasis on examples describing the use of a dedicated microwave synthesizer., (This journal is © The Royal Society of Chemistry 2012)

Heterocycles are important compounds existed in diverse advanced chemicals, functional materials, bioactive molecules and natural products. Different strategies through transition metal‐catalyzed alkyne cyclization have been developed to synthesize various heterocycles. The merger of alkyne cyclization and metal nanoparticle catalysis has emerged as an important approach to diverse heterocycles. By using different kinds of metal nanoparticle catalysts, such as gold, silver, copper and palladium nanoparticles, a number of heterocycles are prepared with high yield and selectivity in a green, sustainable and highly efficient manner. This review summarizes and discusses recent achievements in metal nanoparticle‐catalyzed alkyne cyclization for the synthesis of heterocycles. [ABSTRACT FROM AUTHOR]

The highly efficient construction of complicated heterocyclic frameworks in an atom‐ and step‐economic manner is still one of the cores of synthetic chemistry. Dearomatization reactions show the unique advantage for the construction of functionalized heterocycles and have attracted widespread attention over the past two decades. The metal‐free approach has proved to be a green and sustainable paradigm for the synthesis of spirocyclic, polycyclic and heterocyclic scaffolds, which are widely present in natural products and bioactive molecules. In this review, the advances in the recent six years (2017–2023) in metal‐free dearomatization reactions are highlighted. Emphasis is placed on developments in the field of organo‐catalyzed dearomatization reactions, oxidative dearomatization reactions, Brønsted acid‐ or base‐promoted dearomatization reactions, photoredox‐catalyzed dearomatization reactions, and electrochemical oxidation dearomatization reactions. [ABSTRACT FROM AUTHOR]

A metal‐free expeditious strategy for the divergent synthesis of structurally diverse bicyclic imidazo[1,5‐a]pyrazine and imidazo[1,5‐a][1,4]diazepine scaffolds is disclosed by combining an Ugi four‐component reaction of easily available building blocks and an exo/endo selectivity‐switchable post‐Ugi intramolecular heterocyclization. Using PPh3, the intramolecular umpolung aza‐Michael addition is mediated to selectively generate imidazopyrazinones through a 6‐exo‐dig cyclization, while without PPh3 fused imidazodiazepinones are obtained through a thermal 7‐endo‐dig cyclization in moderate yields. [ABSTRACT FROM AUTHOR]

The use of visible light and photoredox catalysis emerged as a powerful and sustainable tool for organic synthesis, showing the high value of distinctly different ways of bond creation. Indoles and related heterocycles are widely-present in natural products, biologically active compounds, drugs, and agrochemicals. This review summarises the impact of visible light-promoted chemistry on the functionalization of indoles and on the synthesis and modification of indolines, indolin-2-ones, indolin-3-ones, and isatins. Almost 100 references starting from 2012 are cited. [ABSTRACT FROM AUTHOR]

Oxygen‐containing heterocycles are common in biologically active compounds. In particular, phthalan and coumaran cores are found in pharmaceuticals, organic electronics, and other useful medical and technological applications. Recent research has expanded the methods available for their synthesis. This Minireview presents recent advances in the chemistry of phthalans and coumarans, with the goal of overcoming synthetic challenges and facilitating the applications of phthalans and coumarans. O me, O my! Oxygen‐containing heterocycles are common in biologically active compounds. In particular, phthalan and coumaran cores are found in pharmaceuticals, organic electronics, and other useful medical and technological applications. This Minireview presents recent advances in the chemistry of phthalans and coumarans, with the goal of overcoming synthetic challenges and facilitating their application. [ABSTRACT FROM AUTHOR]

In recent years, metallic nanoparticles have been a constant subject of attention for researchers. The transition of metal from microparticles to nanoparticles leads to a substantial change in its physical and chemical properties. Nanoparticles as catalyst in organic reactions provide additional benefits such as catalyst recycling, scale-up of reactions using continuous flow processes, and easy purification of the reaction mixture offering green and cost-effective alternatives. This review highlights some of the significant gold and silver nanoparticle-catalyzed reactions for the synthesis of various heterocyclic compounds. A brief synthetic methodology for different heterocyclic compounds is discussed along with the scope of the reaction. [ABSTRACT FROM AUTHOR]

We report herein an efficient gold(I)-catalyzed post-Ugi domino dearomatization/ ipso-cyclization/Michael sequence that enables access to libraries of diverse (hetero)arene-annulated tricyclic heterocycles. This process affords novel complex polycyclic scaffolds in moderate to good yields from readily available acyclic precursors with excellent chemo-, regio-, and diastereoselectivity. The power of this strategy has been demonstrated by the rapid synthesis of 40 highly functionalized polyheterocycles bearing indole, pyrrole, (benzo)furan, (benzo)thiophene, pyrazole, and electron-rich arene groups in two operational steps. [ABSTRACT FROM AUTHOR]

A high-yielding, temperature switchable divergent approach towards the synthesis of either spiro-indolenines or quinolines is described, starting from easily available indolyl ynones. The application of TFA at rt promotes the dearomatization of the indole, resulting in the formation of the spiro-indolenine, while at higher temperature, rearrangement results in the formation of the quinoline. [ABSTRACT FROM AUTHOR]

An efficient, catalyst-free, microwave-assisted approach has been developed for the synthesis of 2-aryl/alkyl-3-(1H-benzo[d]imidazol-2-yl)-2,3-dihydroquinazolin-4(1H)-one derivatives by condensing 2-aminobenzamides with various aliphatic, aromatic, and heterocyclic aldehydes. This catalyst-free approach exhibited good functional group compatibility and produced the desired products in good to excellent yields in just 10–20 min. This approach can be seen as a better alternative of the metal-catalyzed protocols used for the synthesis of this class of compounds. The formation of desired compound has also been confirmed by X-ray analysis. [ABSTRACT FROM PUBLISHER]

A copper-catalyzed two-step one-pot procedure for the synthesis of thiazolidine-2-thiones has been developed. The process involves a three-component coupling of an alkyne, an aldehyde, and an amine (A3-coupling) followed by trapping the resulting propargylamine with carbon disulfide and subsequent cyclization. [ABSTRACT FROM AUTHOR]

A one-pot sequential A3-coupling-azidation-cyclisation approach leading to potentially biologically active diazepine analogues has been developed. The implementation of the A3-coupling reaction ensures diversity. Attention is given to this so far rarely studied structural motif of fused heterocyclic diazepines. [ABSTRACT FROM AUTHOR]

The amide functionality was used as a remote control for the stereoselective hydro-heteroarylation of acrylamides. This gold-catalyzed carbocyclization provides a diversity-oriented and concise route to biologically important pyrido[3,4-b]indoles. Moreover, the adverse effect of silver salts on this hydro-heteroarylation was also studied. [ABSTRACT FROM AUTHOR]

A new class of 4-oxo-4 H-1-benzopyran derivatives were synthesized and their antiproliferative activity examined against a panel of three human cancer cell lines, that is, breast carcinoma (MDA-MB-468), ovarian adenocarcinoma (SK-OV-3), and colorectal adenocarcinoma (HT-29). Two compounds, that is, 3-hexyl-7,8-dihydroxy-4-oxo-4 H-1-benzopyran and ( E)-ethyl 3-(7-methoxy-4-oxo-4 H-1-benzopyran-3-yl)acrylate were found to be potent against all three cancer cell lines studied at 50 μM concentration. Also, the inhibitory potency of the compounds was evaluated against active Src kinase. A few of these compounds exhibited modest Src kinase inhibitory activity (IC50 = 52-57 μM). studies with respect to the nature and position of substituents on the could be further exploited for the design and development of more potent antiproliferative agents and/or Src kinase inhibitors. [ABSTRACT FROM AUTHOR]

A cascade transformation involving the Ugi reaction followed by 5-endo-dig carbocyclization and retro-Claisen fragmentation providing access to a 1H-pyrrol-2(5H)-one core is described. The operating protocol is very similar to the typical Ugi reaction settings, while the overall outcome results from the application of a 3-substituted propiolic acid and a phenylglyoxal as acid and aldehyde components, respectively. The utility of process is demonstrated through the synthesis of a small library of 5-oxo-2,5-dihydro-1H-pyrrole-2-carboxamides. [ABSTRACT FROM AUTHOR]

[Display omitted] • Evaluating the performance of diaryl-substituted alkynes employed in annulation. • Providing an efficient method to isolate positional isomers. • Accomplishing the synthesis of diverse heterocyclic products. • Furnishing an efficient approach for the total synthesis of rosettacin and a topoisomerase I inhibitor. An intermolecular annulation of 2-acetylenic aldehydes or ketones with O -substituted N -hydroxybenzamides or N -hydroxyacrylamides through rhodium(III)-catalyzed C–H activation for the synthesis of isoquinolones and indolizinones is developed. This reaction features excellent functional-group tolerance and broad substrate scope, including annulation of various heterocyclic substrates. This approach evaluates the chemoselectivity of the reaction when sterically hindered diaryl-substituted alkynes are incorporated. This method also furnishes an efficient approach for the total synthesis of rosettacin and a topoisomerase I inhibitor. [ABSTRACT FROM AUTHOR]

An expedient route for the synthesis of differently substituted 2(1H)-pyrazinones applying a microwave-assisted palladium-catalyzed phosphonium coupling procedure is reported. The method has also been successfully extended to tome other tautomerizable heterocycles for efficient C—C cross-coupling. [ABSTRACT FROM AUTHOR]

[Display omitted] • Developing a rhodium(III)-catalyzed sequential C(sp2)-H activation and C(sp3)-H amination. • Featuring air as the oxidant and various heterocyclic substrates. • Two pathways involved in mechanism via rhodium hydride intermediate. • Furnishing an efficient approach for the total synthesis of rosettacin and a topoisomerase I inhibitor. A novel intramolecular cascade annulation of O -substituted N -hydroxybenzamides for the synthesis of indolizinones triggered by rhodium(III)-catalyzed sequential C(sp2)-H activation and C(sp3)-H amination is developed. This method features air as the oxidant, a broad substrate scope and excellent functional-group tolerance, including various heterocyclic substrates. The applicaton of indolizinone products with aminal functionality is demonstrated by further derivatization. Mechanistic studies and DFT calculations indicate that two pathways are involved in the formation of indolizinones via rhodium hydride intermediate. [ABSTRACT FROM AUTHOR]

A facile catalyst-controlled regioselective post-Ugi intramolecular hydroarylation process was established, which delivers an expedient access to biologically significant heterocycles such as pyrrolopyridinones, pyrroloazepinones, and benzothienopyridines. [ABSTRACT FROM AUTHOR]

A novel and convenient procedure for the synthesis of asymmetrically tri- and tetrasubstituted pyrazines starting from para-methoxybenzyl-protected 3,5-dichloro-2(1H)-pyrazinones was elaborated. The key step is the conversion of the intermediate para-methoxybenzyl-protected thiopyrazinone upon treatment with MeI/I2, into a pyrazine, rendering the chlorine in the C5-position susceptible to substitution. This approach entails the orthogonal introduction of the four substituents of the pyrazine scaffold. The application of microwave irradiation during different steps of the sequence has been shown to be highly valuable for speeding up reactions. [ABSTRACT FROM AUTHOR]

Abstract: Significant improvements in the synthesis of pyrido-fused heterocycles were observed when performing the reaction under solvent-free conditions, applying the tert-amino effect as the key ring closure methodology. An unexpected cyclization of ortho-(1′-azacycloalkyl)benzaldehydes has been studied in water and on solid support. [Copyright &y& Elsevier]

The N-heterocyclic carbene catalyzed chemose-lective C3-aroylation of 3,5-dichloro-2(1H)-pyrazinones with vanous aldehydes is reported. We herein describe results of this remarkable mild and efficient procedure. [ABSTRACT FROM AUTHOR]

The title compounds are prepared by domino cyclization of Ugi-adducts using XantPhos or BINAP as ligand. [ABSTRACT FROM AUTHOR]

Heterocyclic fused α-methylene β-lactams are synthesized by a InCl3-catalyzed intramolecular addition reaction. [ABSTRACT FROM AUTHOR]

Review: 50 refs. [ABSTRACT FROM AUTHOR]

Gold-catalyzed cyclization of Ugi four-component reaction products opens efficient access towards fused nine-membered heterocyclic ring systems. [ABSTRACT FROM AUTHOR]

The article presents chemical equations for the article "Facile Access to Functionalized Spiro[indoline-3,2＇-pyrrole]-2,5＇-diones via Post-Ugi Domino Buchwald-Hartwig/Michael Reaction" by N. Sharma and others, published in the periodical "Organic Letters" in 2014.

The intramolecular hydroarylation of Ugi adducts (V) in the presence of an indium catalyst leads to azepinoindolones (VI), whilst azocineindolones (VII) are obtained using a gold catalyst. [ABSTRACT FROM AUTHOR]

An efficient intramolecular hydroarylation reaction to the corresponding title heterocycles under mild reaction conditions is developed. [ABSTRACT FROM AUTHOR]