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.
169 citations
TL;DR: Interestingly, a detailed investigation of the catalytically active palladium species pointed toward a dual role of the NHC acting as an organocatalyst and forming a novel mixed ligand Pd/NHC/phosphine complex, which represents a new class of chiral palladium catalyst.
Abstract: A comprehensive investigation of the mechanism of the highly enantioselective Pd(PPh3)4/NHC-catalyzed annulation of vinyl benzoxazinanones and enals has been conducted. A study of reaction orders supports the postulated cooperative catalysis. Interestingly, a detailed investigation of the catalytically active palladium species pointed toward a dual role of the NHC acting as an organocatalyst and forming a novel mixed ligand Pd/NHC/phosphine complex. The catalytically active Pd/NHC/phosphine complex represents a new class of chiral palladium catalyst. Remarkably, phosphine plays a crucial role in this transformation. These complexes could be characterized by X-ray crystallographic analysis and employed as catalysts for the enantioselective [4 + 1] annulation reaction of vinyl benzoxazinones and sulfur ylides in good yields and good enantioselectivities.
142 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
142 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.
139 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.
138 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.
135 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.
134 citations
TL;DR: An asymmetric catalytic decarboxylative annulation of 4-ethynyl dihydrobenzooxazinones and carboxylic acids has been established by cooperative copper and nucleophilic Lewis base catalysis.
Abstract: An asymmetric catalytic decarboxylative [4+2] annulation of 4-ethynyl dihydrobenzooxazinones and carboxylic acids has been established by cooperative copper and nucleophilic Lewis base catalysis. A C1 ammonium enolate and copper–allenylidene complex, each catalytically generated from different substrates, underwent a cascade asymmetric propargylation and lactamization process to yield optically active 3,4-dihydroquinolin-2-one derivatives with excellent levels of stereoselectivity (up to 99 % ee, 95:5 d.r.).
131 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...
124 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.
123 citations
TL;DR: Two new gold-catalyzed annulations of isoxazoles with propiolates with Propiolates have been developed, arising initially from two seven-membered heterocyclic intermediates, which then lead to products.
Abstract: Two new gold-catalyzed annulations of isoxazoles with propiolates have been developed. Most isoxazoles follow an initial O attack on the alkyne to afford a [4+1] annulation product. This process results in a remarkable alkyne cleavage of initial propiolates. Unsubstituted isoxazoles proceed through an N attack step to yield formal [2+2+1]/[4+2] annulation products. These two annulation products arise initially from two seven-membered heterocyclic intermediates, which then lead to products.
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: 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.
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: 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.
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: A new procedure for oxidative coupling of aromatic and acrylic acids with alkynes has been developed using abundant, nontoxic, and air stable Cp*Co(III) catalyst, leading to diverse isocoumarins (α-pyranones) in good yields under mild conditions.
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 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 ligand-promoted catalytic [4+2] annulation reaction using indole derivatives and donor-acceptor (D-A) cyclobutanes is reported, thus providing an efficient and atom-economical access to versatile cyclohexa-fused indolines with excellent levels of diastereoselectivity and a broad substrate scope.
Abstract: A ligand-promoted catalytic [4+2] annulation reaction using indole derivatives and donor-acceptor (D-A) cyclobutanes is reported, thus providing an efficient and atom-economical access to versatile cyclohexa-fused indolines with excellent levels of diastereoselectivity and a broad substrate scope. In the presence of a chiral SaBOX ligand, excellent enantioselectivity was realized with up to 94 % ee. This novel synthetic method is applied as a general protocol for the total synthesis of (±)-akuammicine and the formal total synthesis of (±)-strychnine from the same common-core scaffold.
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: 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: 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: 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: 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: A cobalt-catalyzed C-H activation of aryl and heteroaryl sulfonamides and their intermolecular heteroannulation reaction with allenes provides a convergent strategy for the synthesis of biologically interesting heterocyclic scaffolds.
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: 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: This protocol represents a new strategy to access α-imino gold carbenes, which corresponds to an unprecedented intermolecular transfer of N-acylimino nitrenes to ynamides, and proceeds with 100% atom economy, exhibits good functional group tolerance, and can be conducted in gram scale.
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.