Showing papers on "Annulation published in 2017"
TL;DR: This Review summarizes the methods to construct chiral cyclic compounds by gold-catalyzed enantioselective annulations reported since 2005, which have four main types (cycloadditions, cyclizations of C-C multiple bonds with tethered nucleophiles, cycloisomerization or cyclization of enynes, and tandem annulations).
Abstract: In the past decade, there have been many extraordinary advances in the development of gold-catalyzed enantioselective annulations, such as cycloadditions, cyclizations, cycloisomerizations, and tandem annulations, which are of particular interest owing to their potential for rapid construction of optically active hetero- and carbocyclic molecules. This Review summarizes the methods to construct chiral cyclic compounds by gold-catalyzed enantioselective annulations reported since 2005. The Review is organized according to the general annulation types catalyzed by chiral gold complexes or chiral gold salts, which have four main types (cycloadditions, cyclizations of C−C multiple bonds with tethered nucleophiles, cycloisomerization or cyclization of enynes, and tandem annulations), as well as some other strategies. The general reaction mechanisms of each subcategory, key intermediates for some unusual transformations, and the application of several novel ligands and chiral gold salts are also discussed.
206 citations
TL;DR: This work marks the first efficient asymmetric construction of optically enriched eight-membered rings by phosphine catalysis, in excellent yields and with nearly perfect enantioselectivities.
Abstract: The first highly enantioselective phosphine-catalyzed formal [4+4] annulation has been developed. In the presence of amino-acid-derived phosphines, the unprecedented [4+4] annulations between benzofuran/indole-derived α,β-unsaturated imines and allene ketones proceeded smoothly, thus affording azocines, bearing either a benzofuran or an indole moiety, in excellent yields and with nearly perfect enantioselectivities (≥98 % ee in most cases). This work marks the first efficient asymmetric construction of optically enriched eight-membered rings by phosphine catalysis.
184 citations
TL;DR: The authors show the electrocatalytic cross-coupling of phenols and indoles to generate biologically relevant benzofuroindolines in high yields.
Abstract: Intermolecular [3 + 2] annulation is one of the most straightforward approaches to construct five membered heterocycles However, it generally requires the use of functionalized substrates An ideal reaction approach is to achieve dehydrogenative [3 + 2] annulation under oxidant-free conditions Here we show an electrooxidative [3 + 2] annulation between phenols and N-acetylindoles under undivided electrolytic conditions Neither external chemical oxidants nor metal catalysts are required to facilitate the dehydrogenation processes This reaction protocol provides an environmentally friendly way for the selective synthesis of benzofuroindolines Various N-acetylindoles bearing different C-3 and C-2 substituents are suitable in this electrochemical transformation, furnishing corresponding benzofuroindolines in up to 99% yield Electrochemical oxidation provides a green alternative to the use of hazardous chemical oxidants and forcing conditions Here, the authors show the electrocatalytic cross-coupling of phenols and indoles to generate biologically relevant benzofuroindolines in high yields
169 citations
TL;DR: A strategy is reported in which traceless directing groups are used to promote the redox-neutral MnI -catalyzed regioselective synthesis of N-heterocycles in the concise synthesis of the bioactive compound PK11209 and the pharmaceutical moxaverine.
Abstract: An unprecedented strategy using traceless directing groups (TDG) to promote the redox-neutral Mn(I)-catalyzed regioselective synthesis of N-heterocycles is reported. Alkyne coupling partners bearing traceless directing group, which serve as both chelator and internal oxidant, were used to control the regioselectivity of the annulation reactions. This operationally simple approach is highly effective with previously challenging unsymmetrical alkyne systems, including unbiased dialkyl alkynes, featuring switchable regioselectivity, simple conditions, and gram-scale synthesis. The application of this strategy in the concise synthesis of bioactive compound PK11209 and pharmaceutical moxaverine is also described.
163 citations
TL;DR: The use of a chiral SCpRh catalyst enabled the synthesis of a large range of spiropyrazolones with all-carbon quaternary stereogenic centers in up to 99 % yield and 98% ee from readily available substrates.
Abstract: Rhodium-catalyzed C(sp2)−H functionalization reactions of 4-aryl-5-pyrazolones followed by [3+2] annulation reactions with alkynes provide rapid access to highly enantioenriched five-membered-ring 4-spiro-5-pyrazolones. The use of a chiral SCpRh catalyst enabled the synthesis of a large range of spiropyrazolones with all-carbon quaternary stereogenic centers in up to 99 % yield and 98 % ee from readily available substrates.
153 citations
TL;DR: A change in reaction pathway was achieved for the first time by tuning the cyclopentadienyl (Cp) ligand used for the rhodium-catalyzed cyclization of benzamides with conjugated enynones.
Abstract: A change in reaction pathway was achieved for the first time by tuning the cyclopentadienyl (Cp) ligand used for the rhodium-catalyzed cyclization of benzamides with conjugated enynones. Depending on the Cp ligand, the reaction pathway switched between [4+2] and [4+1] annulation. Electronic effects turned out to be crucial for the product distribution. The dichotomy was attributed to the alteration of the Lewis acidity of the resultant Cp-bound rhodium species.
147 citations
TL;DR: The mechanisms and chemo- and regioselectivities of Ru(II)-catalyzed decarboxylative C-H alkenylation of aryl carboxylic acids with alkynes were investigated with density functional theory (DFT) calculations and the polarity of solvent is found to control the chemoselectivity.
Abstract: The mechanisms and chemo- and regioselectivities of Ru(II)-catalyzed decarboxylative C–H alkenylation of aryl carboxylic acids with alkynes were investigated with density functional theory (DFT) calculations. The catalytic cycle involves sequential carboxylate-directed C–H activation, alkyne insertion, decarboxylation and protonation. The facile tether-assisted decarboxylation step directs the intermediate toward the desired decarboxylative alkenylation, instead of typical annulation and double alkenylation pathways. The decarboxylation barrier is very sensitive to the tether length, and only the seven-membered ring intermediate can selectively undergo the designed decarboxylation, suggesting a tether-dependent chemoselectivity. This tether-dependent chemoselectivity also applies to the alkyl tethers. In addition, the polarity of solvent is found to control the chemoselectivity between the decarboxylative alkenylation and [4 + 2] annulation. Solvent with low polarity (toluene) favors the decarboxylation p...
143 citations
TL;DR: Direct and efficient synthesis of 1-naphthols has been realized via Rh(III)-catalyzed C-H activation of sulfoxonium ylides and subsequent annulation with alkynes, where the sulfoxaluminum ylide functioned as a new traceless bifunctional directing group.
140 citations
TL;DR: The N-heterocyclic carbene-catalyzed oxidative [3 + 2] annulation of dioxindole and enals was developed, giving the corresponding spirocyclic oxindole-γ-lactones in good yields with high to excellent diastereo and enantioselectivities as discussed by the authors.
Abstract: The N-heterocyclic carbene-catalyzed oxidative [3 + 2] annulation of dioxindole and enals was developed, giving the corresponding spirocyclic oxindole-γ-lactones in good yields with high to excellent diastereo- and enantioselectivities. The challenging aliphatic enals worked effectively using this strategy. The oxidative cross coupling of homoenolate and enolate via single electron transfer was proposed as the key step for the reaction.
136 citations
TL;DR: Using α,α-difluoromethylene alkyne as a nontraditional one-carbon reaction partner, a synthetically novel method for the construction of isoindolin-1-one derivatives via Rh(III)-catalyzed [4+1] annulation reaction is reported.
Abstract: Using α,α-difluoromethylene alkyne as a nontraditional one-carbon reaction partner, a synthetically novel method for the construction of isoindolin-1-one derivatives via Rh(III)-catalyzed [4+1] annulation reaction is reported. The 2-fold C–F bond cleavage not only enables the generation of desired product under an overall oxidant-free condition but also results in a net migration of carbon–carbon triple bond. In addition, the present reaction protocol exhibits a tolerance of a wide spectrum of functional groups due to the mild reaction conditions employed.
132 citations
TL;DR: Mechanistic studies provided strong support for a facile organometallic C-H manganation, while typical cobalt, ruthenium, rhodium, and palladium catalysts were found completely ineffective.
Abstract: C-H/C-C functionalizations with challenging methylenecyclopropanes (MCPs) were accomplished with a versatile base metal catalyst. Thus, a robust manganese(I) complex enabled the expedient annulation of MCPs by synthetically meaningful ketimines to deliver - upon one-pot hydroarylation - densely substituted polycylic anilines in a step-economical fashion. Mechanistic studies provided strong support for a facile organometallic C-H manganation, while typical cobalt, ruthenium, rhodium and palladium catalyst were found completely ineffective.
TL;DR: To the authors' knowledge, this is the first example in which the NH unit of indole is used as a directing group for an intramolecular C(sp2)-H bond functionalization to give benzo[a]carbazole derivatives.
TL;DR: In this paper, the authors report ruthenium(II)-catalyzed redox-neutral annulation of benzamides and propargyl alcohols, in which propargy alcohols act as one-carbon units.
Abstract: Internal alkynes have been used widely in transition-metal-catalyzed cycloaddition reactions, in which they generally serve as two-carbon reaction partners. Herein, we report ruthenium(II)-catalyzed redox-neutral [4 + 1] annulation of benzamides and propargyl alcohols, in which propargyl alcohols act as one-carbon units. This synthetic utility of propargyl alcohols led to a series of potentially bioactive N-substituted quaternary isoindolinones with moderate to high yields under mild conditions. Without the requirement for an external metal oxidant, this title transformation is compatible with various functional groups, which further underscores its synthetic utility and versatile applicability. In addition, preliminary mechanism experiments have been conducted and a plausible mechanism is proposed.
TL;DR: An electrocatalytic reaction protocol is developed for achieving intramolecular dehydrogenative annulation of N-aryl enamines and good to excellent yields are obtained under oxidant-free and transition-metal-free conditions.
TL;DR: A Lewis-base-catalyzed enantioselective [3 + 3] annulation reaction of Morita–Baylis–Hillman (MBH) carbonates with α-arylidene pyrazolinones is described, affording the pyrazolone-fused spirocyclohexenes bearing an all-carbon quaternary stereocenter in high yields with good to excellent diastereoselectivities and excellent enantiOSElectivities.
Abstract: A Lewis-base-catalyzed enantioselective [3 + 3] annulation reaction of Morita–Baylis–Hillman (MBH) carbonates with α-arylidene pyrazolinones is described, affording the pyrazolone-fused spirocyclohexenes bearing an all-carbon quaternary stereocenter in high yields with good to excellent diastereoselectivities and excellent enantioselectivities.
TL;DR: A novel NHC-catalyzed annulation protocol for the asymmetric synthesis of biologically important β-lactam fused spirocyclopentane oxindoles with four contiguous stereocenters, including two quaternary carbon centers, was developed.
Abstract: A novel NHC-catalyzed annulation protocol for the asymmetric synthesis of biologically important β-lactam fused spirocyclopentane oxindoles with four contiguous stereocenters, including two quaternary carbon centers, was developed Alternatively, spirocyclopentane oxindoles containing an enaminone moiety can be achieved using the same starting materials, isatin-derived enals, and N-sulfonyl ketimines, in the presence of a slightly different NHC catalytic system This switchable annulation strategy enables the selective assembly of both heterocyclic scaffolds with good yields and excellent enantioselectivities for a broad range of substrates
TL;DR: A novel palladium(0)-catalyzed dearomatizing [2+2+1] spiroannulation of 1-bromo-2-naphthols with aryl iodides and alkynes was developed for the rapid assembly of spiro[indene-1,1'-naphthalen]-2'-ones.
Abstract: A novel palladium(0)-catalyzed dearomatizing [2+2+1] spiroannulation of 1-bromo-2-naphthols with aryl iodides and alkynes was developed for the rapid assembly of spiro[indene-1,1′-naphthalen]-2′-ones. This three-component cascade reaction was realized through consecutive Catellani-type C−H activation, unsymmetrical biaryl coupling, alkyne migratory insertion, and arene dearomatization. The potential utility of our method is illustrated by the one-step construction of the polycyclic skeletons of dalesconols A and B from alkyne-tethered aryl iodides and 1-bromo-2-naphthol.
TL;DR: Picolinamide has first been employed as a traceless directing group for the cobalt-catalyzed oxidative annulation of benzylamides with alkynes to synthesize isoquinolines through C-H/N-H bonds activation.
TL;DR: DMSO acted in this reaction not only as solvent but also as one carbon source, thus providing a highly atom-economical and environmentally benign approach for the synthesis of 3-substituted quinolines.
TL;DR: An efficient strategy toward 4-arylquinolines and 4-arylpyrimidines from readily available precursors is described and the application of this strategy to the activation of acetophenone-formamide conjugates toward the synthesis of 4-ARYlpyrimids is also described.
TL;DR: This work describes gold-catalyzed annulations of electron-deficient alkynes with benzisoxazoles to yield quinoline oxides chemoselectively, which afforded various oxygenated tetrahydroquinolines which are present as the cores of many bioactive molecules.
Abstract: This work describes gold-catalyzed annulations of electron-deficient alkynes with benzisoxazoles to yield quinoline oxides chemoselectively. Chemical functionalizations of these resulting azacyclic compounds afforded various oxygenated tetrahydroquinolines which are present as the cores of many bioactive molecules. With the same reactants, a new relay catalysis using gold and zinc(II) catalysts affords highly oxygenated tetrahydroquinoline derivatives stereoselectively.
TL;DR: A mechanism for this multistep domino reaction is proposed on the basis of a 13 C-labeling experiment, according to which an unprecedented chemoselective heterodimerization of two different isocyanides generates an α-amidoketenimine intermediate, which undergoes 1,3-amino migration to form anα-imidoylketene, followed by 6 π electrocyclization.
Abstract: A silver-catalyzed chemoselective [4+2] annulation of aryl and heteroaryl isocyanides with α-substituted isocyanoacetamides was developed for the facile and efficient synthesis of 2-aminoquinolones, naphthyridines, and phenanthrolines. A mechanism for this multistep domino reaction is proposed on the basis of a 13C-labeling experiment, according to which an unprecedented chemoselective heterodimerization of two different isocyanides generates an α-amidoketenimine intermediate, which undergoes 1,3-amino migration to form an α-imidoylketene, followed by 6 π electrocyclization.
TL;DR: Highly efficient methods for the synthesis of 2-arylbenzothiazoles and 2-arylnaphtho[2,1-d]thiazoles have been developed using NH4I or KI as the catalyst to give the annulation products in good to excellent yields with wide functional group tolerance.
TL;DR: In this paper, a palladium-catalyzed formal [4 + 1] annulation reaction was developed for the synthesis of a wide range of polycyclic aromatic hydrocarbons (PAHs) and 1H-indenes with easily available (trimethylsilyl)diazomethane as the carbene source.
Abstract: A highly efficient and operationally simple palladium-catalyzed formal [4 + 1] annulation reaction has been developed. The reaction is featured by the formation of two different C–C bonds on a carbenic center. It represents a concise method for the synthesis of a wide range of polycyclic aromatic hydrocarbons (PAHs) and 1H-indenes with easily available (trimethylsilyl)diazomethane as the carbene source. Metal carbene migratory insertion and C(sp2)–H bond activation are proposed as the key steps in this transformation. The reaction further demonstrates the versatility of the carbene-based coupling in combination with various transition-metal-catalyzed transformations.
TL;DR: This protocol is reported here the first diastereodivergent enantioselective synthesis of bicyclic aminocyclopropanes by lanthanum-catalyzed asymmetric carboamination/annulation of cyclopropenes with aminoalkenes with high chemo- and stereoselectivity.
Abstract: Stereodivergent asymmetric catalysis is an important technology that can allow efficient access to various stereoisomers of a given product with multiple stereocenters from the same set of starting materials, but its application to the synthesis of a highly strained cyclopropane compound has remained unexplored to date. We report here the first diastereodivergent enantioselective synthesis of bicyclic aminocyclopropanes by lanthanum-catalyzed asymmetric carboamination/annulation of cyclopropenes with aminoalkenes. This protocol features 100% atom efficiency, good yield (up to 90%), and high chemo- (up to >20:1) and stereoselectivity (up to >20:1 dr and 99% ee), constituting a unique route for the efficient synthesis of two different diastereoisomers of a given chiral bicyclic aminocyclopropane compound.
TL;DR: In this paper, the asymmetric annulation of O-pivaloyl 1-indolehydroxamic acid with donor/acceptor diazo compounds has been achieved for the first time, to the best of our knowledge, by using a rhodium catalyst embedded in a chiral binaphthyl backbone.
Abstract: The asymmetric C–H annulation of O-pivaloyl 1-indolehydroxamic acid with donor/acceptor diazo compounds has been achieved for the first time, to the best of our knowledge, by using a rhodium catalyst embedded in a chiral binaphthyl backbone. This protocol constitutes a straightforward route for the synthesis of a new family of 1,2-dihydro-3H-imidazo[1,5-a]indol-3-one derivatives having a quaternary carbon stereocenter in high yields and excellent enantioselectivity (up to 98:2 er).
TL;DR: This is the first time that ortho-quinone methides are employed in phosphine-mediated cyclization reactions, and the method led to the formation of chromane derivatives in high yields and excellent enantioselectivity.
TL;DR: In this article, the authors provide molecular insights into an NHC-catalyzed stereoselective annulation reaction between N-methylisatin and an enal leading to spirooxindole lactone in the presence of LiCl as the Lewis acid.
Abstract: An increasing number of examples are now being reported that use chiral N-heterocyclic carbenes (NHCs) in conjunction with Lewis acids to enhance catalytic potential. Herein, we provide molecular insights into an NHC-catalyzed stereoselective annulation reaction between N-methylisatin and an enal leading to spirooxindole lactone in the presence of LiCl as the Lewis acid. Mechanistic features as well as the origin of enantio- and diastereoselectivities of the catalytic reaction have been unraveled using the density functional theory (B3LYP-D3) method. The key mechanistic steps of the reaction are identified to proceed through the formation of a Breslow intermediate between the chiral NHC catalyst and the enal, an enantioselective addition of the re face of this intermediate to the re face of the carbonyl group of N-methylisatin, and an intramolecular proton transfer and lactonization that eventually provide access to (2S,3R)-spirooxindole lactone as the final product. In the most preferred pathway, the Lew...
TL;DR: This protocol presents a rare example of dual sp3 C-H functionalization of tertiary amines with the formation of two different C-C bonds (one sp3 - sp3 bond, one sp2 -sp3 bond).
Abstract: A visible-light-mediated [3+3] annulation of tertiary amines with α-trifluoromethyl alkenes was developed. The reaction offers a direct route to fluorinated tetrahydropyridines and azabicyclo[3.m.1] frameworks under very mild conditions. This protocol presents a rare example of dual sp3 C-H functionalization of tertiary amines with the formation of two different C-C bonds (one sp3 -sp3 bond, one sp2 -sp3 bond). Moreover, two consecutive C-F substitutions in a trifluoromethyl group were achieved in one pot using visible light photoredox catalysis, which enables an unprecedented ring construction.
TL;DR: In this paper, a simple high yielding method to synthesize this scaffold from N-heterocycles was developed, and a wide range of pyridines, quinolines and isoquinolines reacted with donor-acceptor (DA)-aminocyclopropanes via an ytterbium-III catalyzed [3 + 2] annulation reaction to give tetrahydroindolizine derivatives.
Abstract: Many abundant and highly bioactive natural alkaloids contain an indolizidine skeleton. A simple, high yielding method to synthesize this scaffold from N-heterocycles was developed. A wide range of pyridines, quinolines and isoquinolines reacted with donor–acceptor (DA)-aminocyclopropanes via an ytterbium(III) catalyzed [3 + 2] annulation reaction to give tetrahydroindolizine derivatives. The products were obtained with high diastereoselectivities (dr > 20 : 1) as anti-isomers. Additionally, the formed aminals could be easily converted into secondary and tertiary amines through iminium formation followed by reduction or nucleophile addition. This transformation constitutes the first example of dearomatization of electron-poor six-membered heterocycles via [3 + 2] annulation with DA cyclopropanes.