Synthesis of complex heterocycles via Gold(I) catalyzed ammoniumation

Les hétérocycles azotés ont toujours retenu l’attention des chimistes du fait de leurs potentielles activités biologiques mais également pour leurs grandes occurrences dans les produits naturels. De ce fait émerge la nécessité de développer de nouvelles méthodes de synthèse innovantes permettant un accès rapide et efficace à ces hétérocycles. C’est dans cette philosophie que s’inscrivent ces travaux de thèse dont l’objectif est le développement de nouvelles approches basées sur l’utilisation de réactions d’ammoniumation catalysées à l’or(I) afin d’induire des cascades réactionnelles donnant accès à une large variété d’hétérocycles azotés. Ainsi, un motif de base N-sulfonyl-2-(1-propargyl)azétidine a permis d’accéder à une large variété de dérivés pyrroliques et de tétrahydroazépines. L’extension du concept d’ammoniumation lors de l’utilisation des N-(2-alcynylaryl)sulfonyl azétidines a conduit à l’obtention de benzosultames. Un autre défi majeur de la chimie de synthèse moderne est l’obtention de molécules énantiopures. Pour répondre à cette problématique, de nouveaux complexes chiraux NHC platine(II) ont été synthétisés et évalués en tant que catalyseurs sur des réactions de cycloisomérisation.Nitrogen-containing heterocycles have always retained the attention of chemists considering their potent biological properties as well as their large occurrence in natural product structures. Therefore, the development of new innovative synthetic methods that allow a rapid and efficient access to these heterocycles is highly sought. It is in this philosophy that these PhD works take place, whose aims at the development of new approaches based on gold(I) catalyzed ammoniumation reactions in order to trigger cascade reactions and to reach important nitrogen-containing heterocycles. The N-sulfonyl-2-(1-propargyl) azetidine scaffold allows formation of a large variety of pyrroles and tetrahydroazepines derivatives. The extension of the concept of ammoniumation by using N-(2-alcynylaryl)sulfonyl azetidines allowed the formation of benzosultam derivatives. Another major challenge of modern synthetic chemistry is the formation of enantiopur molecules. To reach this goal, new chiral NHC platinum (II) complexes have been synthesized and evaluated as catalysts for cycloisomerization reactions

Synthesis of complex heterocycles via Gold(I) catalyzed ammoniumation

Les hétérocycles azotés ont toujours retenu l’attention des chimistes du fait de leurs potentielles activités biologiques mais également pour leurs grandes occurrences dans les produits naturels. De ce fait émerge la nécessité de développer de nouvelles méthodes de synthèse innovantes permettant un accès rapide et efficace à ces hétérocycles. C’est dans cette philosophie que s’inscrivent ces travaux de thèse dont l’objectif est le développement de nouvelles approches basées sur l’utilisation de réactions d’ammoniumation catalysées à l’or(I) afin d’induire des cascades réactionnelles donnant accès à une large variété d’hétérocycles azotés. Ainsi, un motif de base N-sulfonyl-2-(1-propargyl)azétidine a permis d’accéder à une large variété de dérivés pyrroliques et de tétrahydroazépines. L’extension du concept d’ammoniumation lors de l’utilisation des N-(2-alcynylaryl)sulfonyl azétidines a conduit à l’obtention de benzosultames. Un autre défi majeur de la chimie de synthèse moderne est l’obtention de molécules énantiopures. Pour répondre à cette problématique, de nouveaux complexes chiraux NHC platine(II) ont été synthétisés et évalués en tant que catalyseurs sur des réactions de cycloisomérisation.Nitrogen-containing heterocycles have always retained the attention of chemists considering their potent biological properties as well as their large occurrence in natural product structures. Therefore, the development of new innovative synthetic methods that allow a rapid and efficient access to these heterocycles is highly sought. It is in this philosophy that these PhD works take place, whose aims at the development of new approaches based on gold(I) catalyzed ammoniumation reactions in order to trigger cascade reactions and to reach important nitrogen-containing heterocycles. The N-sulfonyl-2-(1-propargyl) azetidine scaffold allows formation of a large variety of pyrroles and tetrahydroazepines derivatives. The extension of the concept of ammoniumation by using N-(2-alcynylaryl)sulfonyl azetidines allowed the formation of benzosultam derivatives. Another major challenge of modern synthetic chemistry is the formation of enantiopur molecules. To reach this goal, new chiral NHC platinum (II) complexes have been synthesized and evaluated as catalysts for cycloisomerization reactions

Elaboration d'hétérocycles complexes par ammoniumation catalysée à l'or(I)

Nitrogen-containing heterocycles have always retained the attention of chemists considering their potent biological properties as well as their large occurrence in natural product structures. Therefore, the development of new innovative synthetic methods that allow a rapid and efficient access to these heterocycles is highly sought. It is in this philosophy that these PhD works take place, whose aims at the development of new approaches based on gold(I) catalyzed ammoniumation reactions in order to trigger cascade reactions and to reach important nitrogen-containing heterocycles. The N-sulfonyl-2-(1-propargyl) azetidine scaffold allows formation of a large variety of pyrroles and tetrahydroazepines derivatives. The extension of the concept of ammoniumation by using N-(2-alcynylaryl)sulfonyl azetidines allowed the formation of benzosultam derivatives. Another major challenge of modern synthetic chemistry is the formation of enantiopur molecules. To reach this goal, new chiral NHC platinum (II) complexes have been synthesized and evaluated as catalysts for cycloisomerization reactions.Les hétérocycles azotés ont toujours retenu l’attention des chimistes du fait de leurs potentielles activités biologiques mais également pour leurs grandes occurrences dans les produits naturels. De ce fait émerge la nécessité de développer de nouvelles méthodes de synthèse innovantes permettant un accès rapide et efficace à ces hétérocycles. C’est dans cette philosophie que s’inscrivent ces travaux de thèse dont l’objectif est le développement de nouvelles approches basées sur l’utilisation de réactions d’ammoniumation catalysées à l’or(I) afin d’induire des cascades réactionnelles donnant accès à une large variété d’hétérocycles azotés. Ainsi, un motif de base N-sulfonyl-2-(1-propargyl)azétidine a permis d’accéder à une large variété de dérivés pyrroliques et de tétrahydroazépines. L’extension du concept d’ammoniumation lors de l’utilisation des N-(2-alcynylaryl)sulfonyl azétidines a conduit à l’obtention de benzosultames. Un autre défi majeur de la chimie de synthèse moderne est l’obtention de molécules énantiopures. Pour répondre à cette problématique, de nouveaux complexes chiraux NHC platine(II) ont été synthétisés et évalués en tant que catalyseurs sur des réactions de cycloisomérisation

Selective Synthesis of Tetrahydro Oxepines by Cu‐Catalyzed Condensations of Diazomalonates and <i>gem</i>‐Dialkyl Vinyl Oxetanes

Thanks to an unprecedented &lt;i&gt;gem&lt;/i&gt;‐dialkyl substituent effect, an efficient synthesis of tetrahydro oxepine derivatives is achieved by ring expansion of vinyl oxetanes using acceptor (acceptor) diazo reagents under Cu(II)‐catalysis. A large scope of 2‐vinyl oxetanes and either diazo mono or diester reagents give access to a series of functionalized oxepines</p

Dataset for Selective Synthesis of Tetrahydro Oxepines by Cu-Catalyzed Condensations of Diazomalonates and gem-Dialkyl Vinyl Oxetanes

Thanks to an unprecedented gem-dialkyl substituent effect, an efficient synthesis of tetrahydro oxepine derivatives is achieved by ring expansion of vinyl oxetanes using acceptor (acceptor) diazo reagents under Cu(II)-catalysis. A large scope of 2-vinyl oxetanes and either diazo mono or diester reagents give access to a series of functionalized oxepine

Gold(I)-Catalyzed Synthesis of Furopyrans: Insight into Hetero-Diels–Alder Reactions

International audienceWe report herein the synthesis of complex molecules containing furopyran cores through a gold(I)-catalyzed hetero Diels-Alder cascade reaction. During this process, the diene and the dienophile are produced concomitantly by the action of a single catalyst from a single starting material. Moreover, six bonds, four heterocycles and four controlled stereogenic centers are formed in a one-step operation. DFT calculations provide the mechanistic basis of this unprecedented reaction. The last 30 years have witnessed an upsurge in the development of methodologies enabling the synthesis of intricate molecular scaffolds from simple precursors. In addition to these new synthetic strategies, the quest for molecular complexity has often resulted in important fundamental insight into selectivity principles. 1 A particularly promising strategy to rapidly construct complex molecules is to trigger domino reactions that convert simple starting materials into highly sophisticated targets by creating several bonds in a one-pot operation. 2 Achieving complexity with brevity is indeed a key to ideal synthesis. The use of transition metal-catalyzed transformations as part of a domino process considerably decreases the energy cost of the overall transformation and favors highly selective reactions due to the pre-organization of the reactive intermediates around the metallic center. In particular, homogeneous gold(I)-catalyzed reactions have attracted much attention because of the great diversity of original and complex molecules that can be obtained from adequately designed substrates, under mild reaction conditions. 3 Recently, few methodologies have been developed using gold(I)-catalysis in domino processes, including hetero Diels-Alder reactions. The hetero Diels-Alder reaction (HDA) is among the most efficient methods for the synthesis of functionalized heterocycles with control of regio-, diastereo-and enantioselectivity. 4 Most of the gold(I)-triggered HDA reported so far rely on the in situ generation of the diene and/or of the dienophile, starting with two different reagents. 5 However, HDA between diene and dienophile obtained from single starting substrate using gold-catalyst remains elusive. We report herein the synthesis of complex polycyclic molecules 4 containing furopyran cores of interest 6 through a gold(I)-catalyzed domino reaction involving HDA (Scheme 1). During this process, both of the dienophile 2 and the diene 3 are produced concomitantly by the action of a single catalyst from a single starting material 1. To our knowledge, this concept has never been exploited. Moreover, during this transformation , six bonds, four heterocycles and four controlled stere-ogenic centers are formed in a one-step operation with 100% atom economy. DFT calculations provide the mechanistic insight of this unprecedented reaction. Scheme 1. Gold(I)-catalyzed hetero Diels-Alder cascade reaction for the synthesis of furopyrans derivatives 4

Molecular Diversity of Cyclooctatetraenes through Palladium-Catalyzed Cascade Reactions

International audienc

Computational Study of Benzosultam Formation through Gold(I)‐Catalyzed Ammoniumation/Nucleophilic Substitution Reaction

The Au(I)-catalyzed reactions of (2-alkynyl)phenylsulfonyl azetidines bearing terminal and non-terminal alkynes in the presence of methanol as protic nucleophile to form benzosultams derivatives were studied by density functional theory (DFT) calculations. Our study highlights that gold(I) catalyzed nucleophilic addition of the nitrogen on the alkyne is favored over the direct ring opening of the azetidine by methanol, confirming the ammonium-based mechanism. In addition, the reverse regioselectivity observed experimentally where non-terminal alkynes favors the formation of 6-endo-dig-benzosultams while terminal alkynes favor 5-exo-dig products is also explored through two different scenarios. The first one embraces the classical activation of the alkyne by a single Au(I) species while the second one tackles the formation of a σ,π-digold acetylide complex. Calculations identify both pathways as competitive although only mono Au(I) complexes can lead to final products, in good agreement with experimental observation. Further details on the importance of the presence of an excess of the protic nucleophile on the protodemetallation step and the final aminal formation is also discussed

Dataset of Spirocyclic Amide Acetal Synthesis by [CpRu]-Catalyzed Condensations of α‑Diazo-β-Ketoesters with γ-Lactams

AbstractThe synthesis of spirocyclic amide acetals (33-93%) has been achieved through Ru(II)-catalyzed condensations of N-carbamate protected pyrrolidinones with metal carbenes derived from α‑diazo-β-ketoesters. Thanks to the mildness of the diazo decomposition conditions induced by a 1:1 combination of [CpRu(MeCN)3][BArF] and 1,10-phenanthroline, the formation of the sensitive products is possible. Full characterization of this carbonyl-ylide mediated process is provided by DFT calculations