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A gold(I)-catalyzed cascade intramolecular cyclization of Ugi adducts for the divergent construction of quinazolinone and ampakine analogues has been developed in a rapid, highly efficient and step-economical manner. This protocol shows high yields, excellent functional-group tolerance, broad substrate scope and excellent chemo- and regioselectivity. The practicality of this strategy is further demonstrated by a scale-up reaction. Diverse oligopeptides are also found to be well tolerated, affording polycyclic products decorated with a peptide chain.

A concise and flexible procedure for the synthesis of highly functionalized N-heterocyclic 1,6-annulated 2-pyridones and 2,3-annulated 4-pyrimidinones has been elaborated through a gold-catalyzed tandem hydroamination/cycloisomerization cascade. This novel and highly efficient method allows the rapid construction of these diverse N-heterocyclic scaffolds starting from readily available building blocks, and shows a wide scope and good functional group tolerance. The total synthesis of (±)-seco-antofine and (±)-septicine were realized employing this strategy.

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.)

Cationic gold-catalyzed cycloisomerizations of propargylureas, derived in situ from secondary propargylamines and aryl or alkyl isocyanates, have been studied. The reaction outcome was found to be different from what was previously observed for the tosyl isocyanate-derived ureas in terms of both regio- and chemoselectivity. As a result, the current protocol offers efficient access to the 3,4-dihydropyrimidin-2(1H)-one core through the 6-endo-dig N-cyclization.

A gold-catalyzed regioselective tandem cyclization of N-propynylbutynamide via Csp(3)-H functionalization has been described, providing a distinctive methodology for the architecture of cyclopentapyridinones as well as spirocyclopentapyridinones.

A post-Ugi indium(III)- and gold(I)-mediated regioselective intramolecular hydroarylation for the synthesis of azepino- and azocino-[c,d]indolones is described.

A novel diversity-oriented post-Ugi/gold(I)-catalyzed heteroannulation process for the synthesis of imidazo[1,4]diazepin-7-ones is elaborated. The scope and limitations of the protocol are discussed.

A regioselective approach for the synthesis of pyrrolopyridinones and pyrroloazepinones is reported employing an Ugi reaction followed by a gold(I) or platinum(II) catalyzed intramolecular hydroarylation.

The Ugi reaction has become one of the highly explored reactions for the formation of multifunctional adducts, due to the mild reaction conditions, wide scope and high variability. By carefully selecting the starting four components, Ugi‐adducts could undergo different kinds of post‐transformations for the synthesis of bioactive heterocycles, natural products and macrocycles. Considering the significance of polycycles, diverse post‐Ugi transformations have been developed over the years for constructing structurally novel polycycles. In this account, we summarize important efforts for the synthesis of polycyclic N‐heterocycles via post‐Ugi cyclizations from the Van der Eycken laboratory onwards 2016. With the aid of transition metal catalysis from gold, rhodium, silver and palladium, as well as metal‐free strategies, versatile polyheterocycles are prepared with high efficiency and step‐economy. [ABSTRACT FROM AUTHOR]

Over the years, gold catalysis has materialized as an incredible synthetic approach among the scientific community. Due to the trivial reaction conditions and great functional compatibility, these progressions are synthetically expedient, because practitioners can implement them to build intricate architectures from readily amassed building blocks with high bond forming indices. The incendiary growth of gold catalysts in organic synthesis has been demonstrated as one of the most prevailing soft Lewis acids for electrophilic activation of carbon-carbon multiple bonds towards a great assortment of nucleophiles. Nowadays, organic chemists consistently employ gold catalysts to carry out a diverse array of organic transformations to build unprecedented molecular architectures. Despite all these achievements and a plethora of reports, many vital challenges remain. In this account, we describe the reactivity of various gold catalysts towards cyclization processes developed over the years. These protocols give access to a wide scope of polyheterocyclic structures, containing different medium-sized ring skeletons. This is interesting, as the quest for highly selective reactions to assemble diversely functionalized products has attracted much attention. We envisage that these newly developed chemo-, regio-, and diastereoselective protocols could provide an expedient route to architecturally cumbersome heterocycles of importance for the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

A post-Ugi gold-catalyzed regioselective intramolecular carbocyclization strategy is reported. A better cationic gold system, compared to our previous report, has been optimized and utilized. The method presented exhibits excellent functional group compatibility including bulky substitutions on alkynes and allows the direct access to indoloazepinones and indoloazocinones in good to excellent yields. [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 highly efficient approach for the regioselective construction of fused nine-membered rings (diazoninone framework) was developed by employing sequential Ugi and gold-catalyzed intramolecular hydroarylation reactions. The scope of this intramolecular cyclization has been demonstrated. [ABSTRACT FROM AUTHOR]

A post-Ugi late-transition-metal-catalyzed intramolecular hydroarylation approach opens a new gateway for the synthesis of diversely substituted pyrrolopyridinones, pyrroloazepinones thiophenoazepinones, azepinoindoles, and azepinobenzothiophenes applying mild reaction conditions. A detailed investigation of the scope of this strategy is discussed. [ABSTRACT FROM AUTHOR]

A diversity-oriented approach comprising a Ugi four-component reaction and gold(I)-catalyzed hydroarylation under very mild reaction conditions has been elaborated. This gives direct access to the synthesis of biologically important heterocycles such as pyrrolopyridines, pyridoindoles, and azepinoindoles in very good yields. The influence of the nucleophilicity of the heterocycle and the mode of ring closure are discussed. [ABSTRACT FROM AUTHOR]

A comparative study on transition metal-catalyzed cycloisomerizations of propargylic ureas derived in situ from secondary propargylic amines and tosyl isocyanate was performed. The influence of catalytic system on the reaction outcome was thoroughly studied on two model examples resulting in the establishment of two selective protocols for both O- and N-cyclizations. The application of cationic gold(I) catalysis generally resulted in a formation of oxazolidin-2-imines as major products while the application of silver(I) triflate selectively provided the corresponding imidazolidin-2-ones. An attempt to rationalize the observed chemoselectivity is described. The scope of both processes was demonstrated through the use of variously substituted secondary propargylic amines. [ABSTRACT FROM AUTHOR]

• A gold-catalyzed cascade annulation of peptidomimetics and oligopeptides for the synthesis of highly functionalized pyrrolo[1,2- b ]isoquinolines. • Tandem 6-endo-dig cyclization/enyne cycloisomerization/1,2-migration cascade. • Excellent chemo- and regioselectivity, functional group tolerance. A chemo- and regioselective gold-catalyzed tandem 6-endo-dig cyclization/enyne cycloisomerization/1,2-migration process for the synthesis of decorated peptidomimetics is developed. Various migrating groups such as aryl, heteroaryl and alkyl are tolerated in this method under mild conditions. This protocol is successfully utilized to modify various oligopeptides, including substrates bearing the drug amantadine, in a rapid and step-economical manner through the combination with the Ugi reaction. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: A gold-catalyzed regioselective heteroannulation strategy has been developed for the concise and efficient synthesis of imidazo[1,2-a]pyrazinones. The protocol allows the introduction of diversity via the application of substituted propargyl amines or via Suzuki-coupling of the generated imidazo[1,2-a]pyrazinones with various (het)aryl boronic acids. [Copyright &y& Elsevier]

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]