Gold(I)-Catalyzed Domino Reaction : An Access to furooxepines

International audienceWe report herein the synthesis of [7,5]-fused bicyclic acetals, also named furooxepines derivatives through a gold(I)-catalyzed domino reaction. During this transformation, two molecules of homopropargyl alcohol react together, in a sequence including an intramolecular hydroalkoxylation, condensation, a 1,6-enyne cycloisomerization, acetalization and an isomerization. This gold(I)-catalyzed domino reaction allow the formation of three bonds, two heterocycles and a tetrasubstituted carbon stereocenters in a one-step operation with 100% atom economy. Post-functionalizations allow the formation of tetrahydrofurans

Recent Contributions to Hetero Diels-Alder Reactions

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Synthesis of Polyheterocyclic Tropones by [2 + 2 + 2 + 1] Carbonylative Cycloaddition of Triynes

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Solvent Effect in Gold(I)-Catalyzed Domino Reaction: Access to Furopyrans

International audienceWe report an efficient synthesis of furopyrans through a gold(I)-catalyzed domino reaction. Starting from the same source, and by changing the solvent of the reaction, two classes of furopyrans are accessible. During this one-step process, which takes place in DMF, two bonds and two heterocycles are formed. DFT calculations furnish the mechanistic understanding of this transformation. The sequence includes a 5-endo-dig cyclization, a regioselective 8-endo-dig cyclization, a retro 8p and a 6p electro-cyclization

Synthesis of Aromatic Rings Embedded in Polycyclic Scaffolds by Triyne Cycloaddition: Competition between Carbonylative and Non-Carbonylative Pathways

Cycloadditions have emerged as some of the most useful reactions for the formation of polycyclic compounds. The carbonylative cycloaddition of triynes can lead to carbonylative and non-carbonylative competitive pathways, each leading to the formation of an aromatic ring. We report herein the one-pot synthesis of fully- and unsymmetrically-substituted tetracyclic 6,5,7,5-troponic and 6,5,6,5-benzenoid scaffolds using pre-organized triynes showing the competition between these two pathways

Carbonylative cycloaddition for the synthesis of medium-sized carbo- and heterocycles

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Synthesis of Medium-Sized Heterocycles by Transition-Metal-Catalyzed Intramolecular Cyclization

Medium-sized heterocycles (with 8 to 11 atoms) constitute important structural components of several biologically active natural compounds and represent promising scaffolds in medicinal chemistry. However, they are under-represented in the screening of chemical libraries as a consequence of being difficult to access. In particular, methods involving intramolecular bond formation are challenging due to unfavorable enthalpic and entropic factors, such as transannular interactions and conformational constraints. The present review focuses on the synthesis of medium-sized heterocycles by transition-metal-catalyzed intramolecular cyclization, which despite its drawbacks remains a straightforward and attractive synthesis strategy. The obtained heterocycles differ in their nature, number of heteroatoms, and ring size. The methods are classified according to the metal used (palladium, copper, gold, silver), then subdivided according to the type of bond formed, namely carbon–carbon or carbon–heteroatom

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

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