Gold-Catalyzed Cascade Reactions of 4H-Furo[3,2-b]indoles with Allenamides: Synthesis of Indolin-3-one Derivatives

Merging the ability of cationic gold(I) catalysts to activate unsaturated \u3c0-systems with the electrophiles driven ring-opening reactions of furans, we describe a new approach to 2-spiroindolin-3-ones from 4H-furo[3,2-b]indoles. The reaction occurs through a cascade sequence involving addition of a gold-activated allene to the furan moiety of the starting furoindole followed by a ring-opening/ring-closing event affording 2-spirocyclopentane-1,2-dihydro-3H-indolin-3-ones in moderate to good yields

Axially Chiral Triazoloisoquinolin-3-ylidene Ligands in Gold(I)-Catalyzed Asymmetric Intermolecular (4 + 2) Cycloadditions of Allenamides and Dienes

The first highly enantioselective intermolecular (4 + 2) cycloaddition between allenes and dienes is reported. The reaction provides good yields of optically active cyclohexenes featuring diverse substitution patterns and up to three stereocenters. Key to the success of the process is the use of newly designed axially chiral N-heterocyclic carbene–gold catalystsThis work was supported by the Spanish MINECO (SAF2010-20822-C02, CTQ2010-15297, CTQ2010-14974, and Consolider Ingenio 2010 CSD2007-00006), the ERDF funds, the Xunta de Galicia (INCITE09209084PR, GRC2010/12), and the Junta de Andalucía (2008/FQM-3833 and 2009/FQM-4537, predoctoral fellowship to F.G.-C). H.F. acknowledges the Fundação para a Ciência e Tecnologia (FCT, Portugal) and POPH/FSE for a Ph.D. grant (Grant SFRH/BD/60214/2009)S

Palladium-catalyzed domino carbopalladation/5-exo-allylic amination of \u3b1-amino allenamides: an efficient entry to enantiopure imidazolidinones

Allenamides of alpha-amino acids were converted into enantiopure 2-vinylimidazolidin-4-ones by a carbopalladation/exo-cyclization process. The products were obtained in 2.5:1-5.5:1 dr, with 94-99% ee. The palladium-catalyzed carbonylative cyclization of the same substrates afforded enone structures. Starting from properly substituted allenamides, an intramolecular carbopalladation followed by intramolecular amination gave rise to tricyclic fused-ring imidazolidinones

Cycloaddition chemistry of allenamides

Allenamides are electron deficient allenamine equivalents that can participate in a range of cycloaddition events giving rise to novel heterocycles and diverse molecular architectures contained within natural products. This review summarizes some of the recent research in this area, with particular reference to predicting the stereochemical outcomes of such transformations and highlighting recent applications of allenamides in cycloaddition transformations which showcase the utility of this under-utilized synthon

Development of photoredox-catalysed transformation of enamides and allenamides

Enamides and allenamides are two versatile functional groups that offer a wide variety of alternatives for the inclusion of nitrogen-based moiety into an organic system. Nitrogen-containing structures are prevalent among medicinally interesting natural and unnatural products and, thus, are useful in developing new therapeutics. Their chemical utilities have been exploited by a number of research groups. They represent interesting functional groups and useful in organic synthesis. Photoredox catalytic approach was develop to synthetically transform enamides into useful products, N-acyl-N -aryl-N,N -aminals. A novel approach using iridium polypyridyl complex photoredox catalyst to initiate a three-component domino transformation of enamides to N-acyl-N -aryl-N,N -aminals via photoredox catalysed β-alkylation of enamide intermediates and their subsequent trapping with an arylamine was successfully developed. The N-acyl-N′-aryl-N,N′-aminal structural motif is prevalent within a wide range of biologically important compounds and have attracted considerable attention as building blocks for the synthesis of drug candidates. This method uses the addition of a radical precursor to an enamide, with subsequent interception of the cationic iminium intermediate with an arylamine. The reaction was found to be compatible with both electron-rich and electron-deficient arylamines, and moderate to good levels of diastereoselectivity were attained using a chiral enamide. The N-acyl-N -aryl-N,N -aminals formed were used as precursors to synthesis of valuable γ-lactams building blocks under a mild condition by cyclization. The γ-lactams were obtained by intramolecular cyclization of the N,N -aminals with the lone pair of the nitrogen atom of the arylamine as the nucleophilic centre attacking the electrophilic carbon of the carbonyl carbon of the ester in the molecule. This is a novel synthetic route to these valuable γ-lactams. The photoredox reaction procedure developed was also applied on allenamides. There are limited reports of radical reactions on allenamides, the major and seemingly single intermolecular radical cyclization involving allenamides was the one reported by Hsung. There are no reports of radical photoredox reactions on allenamides in the literature. The addition reaction was initiated by the electrophilic malonate radical generated by irradiation with blue light in the presence of iridium photoredox catalyst. The malonate radical attacked the central carbon of the allenic group which led to the formation of β-alkyl allenamide radical that was oxidized to an iminium ion intermediate. The iminium intermediate was subsequently trapped with an arylamine giving rise to α,β-addition product (N-acyl-N -aryl-N,N -aminals) with exo-methylene or β,γ-addition product leading to the formation of double bond substituted enamides. It was found that the α,β-adduct product is more favourable, however, the alternative product was formed when the α-position is sterically hindered by the substituents on the allenamide or the arylamine nucleophile

[4+2] and [4+3] catalytic cycloadditions of allenes

This feature review describes the development of catalytic [4+2] and [4+3] cycloadditions of allenes, as efficient and practical methodologies for assembling six and seven-membered cyclic systems. The different methodologies have been classified depending on the type of key reactive intermediate that was proposed in the catalytic cycleS

Allenes and Derivatives in Gold(I)- and Platinum(II)-Catalyzed Formal Cycloadditions

Conspectus Cycloaddition reactions, by involving the formation of at least two bonds and one cycle in a single operation, represent one of the more practical ways to assemble carbo- and heterocyclic structures from simple acyclic precursors. Especially appealing are formal cycloadditions promoted by transition metals, owing to the ability of these reagents to open mechanisms that are not accessible using classical chemistry. Therefore, along the years, a great variety of annulations based on first-, and particularly second-row transition metals have been discovered. Most of these reactions involve inner sphere mechanisms, with the metal participating via standard oxidative addition or reductive elimination processes. Curiously, metals of the third row like platinum and, especially, gold remained largely unexplored, likely because of the belief that they were inert and expensive. However, from the beginning of this century, many groups realized that these metals can open very interesting mechanistic scenarios and promote novel types of transformations. In particular, the π-acidic, carbophilic behavior of gold(I) complexes, together with the possibility of tuning their reactivity using designed ligands, has triggered important activity in the field. Many gold-catalyzed transformations involved addition or cycloisomerization processes, but during recent years, there have been also important advances in the development of formal cycloaddition reactions. While many of these reactions rely on the activation of alkynes, there has been an increasing number of reports that exploit the peculiar reactivities of allenes and derivatives. In this Account, we present recent efforts on the development of platinum- and gold-catalyzed formal cycloadditions of allenes. For the sake of simplicity, we only include annulations initiated by a direct metal-promoted activation of the allene moiety. Thus, alternative Pt- or Au-catalyzed reactions wherein the allene does not interact with the metal catalyst are not covered. Upon activation by the metals, allenes generate allyl-cation alkenylmetal species that can behave as 1,2- or 1,3-carbon dipoles in cycloaddition processes. Especially relevant is the reactivity of allenamides. The presence of the amide substituent provides for the generation of gold intermediates with a good balance of reactivity and stability, which can therefore react with the corresponding partners in a controlled manner. Moreover, despite the difficulties associated with the transfer of stereochemical information from chiral linear gold(I) complexes, a variety of enantioselective gold-catalyzed annulations have been discovered. This Account is organized considering the number of atoms engaged in the annulation process, and when possible, we present the results in a chronological orderFinancial support from the Spanish MINECO (SAF2016-76689-R, CTQ2017-84767-P, FPU fellowship to I.V), the Xunta de Galicia (ED431C 2017/19, 2015-CP082, Centro Singular de Investigación de Galicia accreditation 20162019 ED431G/09), the ERDF, and ERC (Adv. Grant No. 340055) is acknowledgedS

Gold(I)‐Catalyzed Cascade Cycloadditions between Allenamides and Carbonyl‐Tethered Alkenes: An Enantioselective Approach to Oxa‐Bridged Medium‐Sized Carbocycles

This is the peer reviewed version of the following article: Faustino, H. , Alonso, I. , Mascareñas, J. L. and López, F. (2013), Gold(I)‐Catalyzed Cascade Cycloadditions between Allenamides and Carbonyl‐Tethered Alkenes: An Enantioselective Approach to Oxa‐Bridged Medium‐Sized Carbocycles. Angew. Chem. Int. Ed., 52: 6526-6530, which has been published in final form at https://doi.org/10.1002/anie.201302713. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsGold standard: Allenamides react with aldehydes or ketones having γ, δ, or ε alkenyl groups, upon activation with suitable gold catalysts, to provide oxa-bridged systems containing seven- to nine-membered carbocycles, in a formal cascade cycloaddition. By using chiral phosphoramidite/gold or bisphosphine/gold catalysts it is possible to obtain the oxa-bridged seven- and eight-membered rings with good to high enantioselectivityThis work was supported by the Spanish MINECO, (SAF2010‐20822‐C02‐01/02, and Consolider‐Ingenio 2010 CSD2007‐00006), ERDF funds, and Xunta de Galicia (INCITE09209084PR, GRC2010/12). H.F. acknowledges the Fundação para a Ciência e Tecnologia (Portugal) and POPH/FSE for a PhD grant (SFRH/BD/60214/2009)S