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Gold‐Catalyzed Functionalization Reactions of Indole
No full textThis review summarizes the progress achieved in the last fifteen years by application of homogeneous gold catalysis in the field of indole functionalization. Several electrophilic species obtained through gold‐catalyzed π‐activation have in fact been found to react with the nucleophilic positions of indole, thus allowing its efficient manipulation. In order to furnish a complete and clear overview on the role of the catalyst, the review is organized from the perspective of the gold‐activated substrate that is reacting with the indole. In addition, in view of the ability of gold to catalyze tandem and cascade reactions, a separate section describes tandem/cascade protocols useful for the synthesis of complex polycyclic indole derivatives. Finally, gold catalysis has also been employed for the synthesis of indole‐based natural products. For this reason, a dedicated section collects all the work in which the key step to obtain these complex indoles is represented by a gold‐catalyzed reaction
Gold(I)-catalyzed [4+2] cycloaddition reactions of vinylindoles and allenes
Full text linkCarbazole and tetrahydrocarbazole rings are the key structural motif in a great number of biological active molecules, including natural alkaloids and synthetic products. For this reason, strategic syntheses of these indole derivatives are highly required, in particular when based on asymmetric methodologies. In this research field, 2- and 3-vinylindoles have become versatile 4C building blocks for the synthesis of complex tetrahydrocarbazole derivatives by means of [4+2] cycloadditions. Among dienophiles, it has been shown that gold activated allenes could participate in [4+2] processes and we published the first example of gold catalyzed reaction of 2- and 3-vinylindoles with allenamides and allenyl esters. In this latter work we reported also some preliminary investigations on enantioselective synthesis of tetrahydrocarbazoles, by conducting the reaction in the presence of a chiral gold(I) phosphoramidites. Prompted by these results and taking into account the importance of asymmetric tetrahydrocarbazole synthesis, we next explored the reactivity of 3/2-substituted-2/3-vinylindoles with N-allenamides under chiral gold(I) catalysis for the synthesis of a new series of dearomatized indoles bearing a quaternary C4a/C9a stereocenter (Scheme 1). The results obtained in this work will be presented in the context of our investigations on gold(I) catalyzed syntheses of tetrahydrocarbazoles
2- and 3-vinylindoles as 4π components in cycloaddition reactions
Full text link[4+2] cycloaddition reactions are among the most useful transformations in synthetic organic chemistry. They are a widely used method for the assembly of simple and complex six membered carbo- and heterocyclic compounds. The reaction is modulated by the substituents on both the diene and the dienophile partners and by the design of different catalytic species. In particular, among dienes, internal-external ring dienes represent a class of very useful and versatile molecules and their participation as 4π-components in cycloaddition reactions allows for the construction of complex polycyclic compounds. Taking a peak to the structure of 2- and 3-vinylindoles, it is easy to claim that they pertain to this class of molecules and, during the last ten years we developed several strategies to access carbazole derivatives through [4+2] cycloaddition reactions of vinylindoles with a plethora of unsaturated compounds. In particular, starting from Lewis acids catalyzed reactions with cyclic and acyclic dienophiles,1 we explored the possibility of using cationic gold(I) species to promote the reaction of vinylindoles with unactivated π-systems as dienophiles. (e.g. N-allenamides, propargylic esters). In this way we were able to construct complex and intriguing architectures in a stereocontrolled fashion.2 In addition, considering the importance of asymmetric syntheses of carbazole derivatives, we investigated the reactivity of 3/2-substituted-2/3-vinylindoles with N-allenamides under chiral gold(I) catalysis for the synthesis of a new series of dearomatized indoles bearing a quaternary C4a/C9a stereocenter.3 The results obtained in our last studies on [4+2] cycloaddition reaction with vinylindoles will be discussed with particular focus on the choice of catalysts and on the reaction mechanisms
Domino Addition/Cycloisomerization Reactions of 2-Alkynyl-Arylaldehydes: Silver Catalyzed Synthesis of 1,3-Dicarbo-Substituted Isochromenes
Full text linkOne of the most efficient methods for the construction of 1-substituted isochromenes (and related heteroaryl compounds) is the metal catalyzed regioselective domino cycloisomerization/nucleophilic addition reaction of a 2-alkynyl(hetero)arylaldehyde in the presence of a suitable nucleophile.(1) The reaction with oxygen nucleophiles is the probably the most studied one. Several metal catalyst have been used, and our group recently gave a contribution in the field of silver catalyzed(2) synthesis of 1-alkoxyisochromenes.(3) Conversely, the reaction with carbon nucleophiles, and in particular with enolizable carbonyl compounds, is relatively less investigated.(4) We report here our recent results regarding the silver catalyzed synthesis of 1,3-dicarbo-substituted isochromene derivatives starting from 2-alkynyl(hetero)arylaldehydes and enolizable carbonyl compounds.(5) The reaction proceeded in a cascade fashion under mild reaction conditions with absolute regioselectivity and moderate-to-good yields. In some cases, the reaction produced unexpected diastereoisomeric couple of homodimeric products. The divergent formation of the 1-carbosubstituted isochromenes and the alternative homodimeric products has been tentatively explained by some experiments and two conceivable competitive paths have been proposed
A new synthesis of indolin-3-one derivatives
Full text linkIndolin-3-one scaffold occur in the core structure of a large number of compounds with pharmaceutical and biological importance. In particular, 2-spirocyclopentane-indolin-3-ones are reported in literature as components of several alkaloids with interesting biological properties or as intermediates for the synthesis of active pharmaceutical compounds. Moreover, they share with the corresponding 2-methylene-indolin-3-ones emergent applications as functional fluorescent dyes. Taking into account these premises and our experiences in the transition metal catalyzed synthesis and functionalization of indole derivatives, we decided to explore the reactivity of 4H-furo[3,2-b]indoles in the presence of gold(I) activated π-systems for the synthesis of new classes of indolin-3-one derivatives. In particular, employing N-allenamides or propargylic esters, a careful screening of the gold(I) catalysts allowed for the synthesis of two different classes of indolin-3-ones through gold-promoted cascade sequences involving functionalization at the furan moiety followed by a ring-opening event. The obtained results will be presented with particular focus on the optimization of catalytic reaction conditions and on reaction mechanism
Gold-catalyzed synthesis and functionalization of heteroarenes
Full text linkThis work describes the results obtained from the study of gold-catalyzed synthesis or functionalization reactions or heteroarenes. The work is presented in four different chapters. The first chapter summarizes the most representative reactivity trends in the field of gold catalysis and serves as general introduction. The second chapter is focused on the cycloaddition reaction of 2-vinylindoles with enones towards the preparation of tetrahydrocarbazole derivatives. This process has been studies using classic Lewis acids and gold complexes as catalysts. According to the results, gold catalysts proved more efficient to accomplish the transformation. In the third chapter, a study on gold-catalyzed cycloaddition reactions of 2-vinylindoles with allene derivatives is presented. This work has allowed to identify two different reaction pathways, a formal 4+2 cycloaddition and a multicomponent reaction, both leading to different tetrahydrocarbazole derivatives. The reaction outcome can be controlled with the judicious choice of the reaction conditions. The forth chapter is devoted to the study of gold- and to less extend silver-catalyzed reactions of indoles with dehydroaminoacis. This study has enabled the discovery of a new reactivity of this substrates. The reaction involves the formation of ¿-indolylacrilate derivatives
Gold(I) and Gold(III) catalyzed cycloaddition/cyclization reactions of vinylindoles with allenes
Full text linkIn the last year we developed several strategies to access carbazole derivatives through [4+2] cycloaddition reactions of 2-vinylindoles with allenes under gold catalysis. Application of cationic gold(I) and gold(III) catalysts as -activators allowed for the chemo-, regio- and diastereoselective construction of complex and intriguing architectures. More recently we are focusing on the enantioselective version of these and related reactions. In particular, we are currently studying the enantioselective version of our cascade reaction between 2-vinylindoles and propargyl esters and between a new class of 2-vinylindoles bearing a methyl group at C-3 position with allenamides for the synthesis, respectively, of enantioenriched tetrahydrocarbazoles and dearomatized indole derivatives. A complete survey of catalyst/ligand screening as well as scope and proposed reaction mechanisms will be reported
Synthesis of indole-fused 1,4-diazepinones through photocatalytic strategies
No full textOver the last years, photoredox catalysis has spread as an essential tool to generate radicals under mild and selective conditions and it was applied for the synthesis of heterocyclic structures via cascade cyclizations (10.1021/acs.chemrev.0c00030). Considering this background and the interest of our group in the synthesis of polycyclic indoles, we developed a synthesis of indole-fused 1,4-diazepinones through a cascade radical addition on the C–C double bond of N-indolyl phenylacrylamides, followed by cyclization at indole C2-position (10.1002/adsc.202300708)
Copper(I)- catalyzed regio- and stereoselec6ve synthesis of cyclopropyl vinylindolines
Full text linkThe functionalization of indole core is an interesting research field because the indole moiety is present in a huge number of bioactive natural products and pharmaceutical compounds. For this reason, the proposal of new methodologies for indole synthesis and functionalization is still of great interest in synthetic organic chemistry. In the context of our studies on metal-catalyzed cycloaddition reactions of vinylindoles and on functionalization of indole core, we decided to investigate the reactivity of 2-vinylindoles with diazo compounds. We envisioned in this way to functionalize these indole derivatives by means of a new reaction pattern. Thus, the reaction between 2-vinylindole and ethyl diazoacetate was conducted in the presence of a copper(I) complex and led to a series of cyclopropyl vinylindolines with satisfactory yields and with complete regio- and diasteroselectivity (Figure 1). Optimization of conditions, scope and proposed mechanism of the reaction will be illustrated in the poster, together with preliminary results on an enantioselective version
Gold catalyzed asymmetric synthesis of axially chiral indole-fused diazocines
Full text linkAtropisomerism, also called axial chirality, is a particular kind of chirality in which the rotation of a σ bond
is constrained because of the steric or electric effects of bulky substituents. The main difference between
classical stereoisomers and atropisomers is that classical stereocenters are often stable and racemize via a bondbreaking, while racemization for axially chiral compounds is possible through an intramolecular dynamic
process that simply involves bond rotation.1 This time-dependent chirality shows great potential for drug
development and has been observed in natural products. In addition many chiral catalysts and ligands that are
frequently used in asymmetric synthesis are axially chiral compounds.
2 Among these substrates, axially chiral
indole derivatives have been recognized as an important class of five-membered heterobiaryls, because of their
presence in some natural alkaloids, chiral phosphine ligands and bioactive molecules.
3 Taking into account
these premises, this poster will deal with our recent developments in the gold catalyzed asymmetric synthesis
of axially chiral indole-fused diazocines. In particular, optimization of catalytic conditions and preliminary
substrate scope of the reaction will be presented together with a mechanistic proposal
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