Showing papers on "Annulation published in 2014"
TL;DR: The Cp*Co(III) catalysis was also suitable for simple alkenylation process of N-carbamoyl indoles, and broad range of alkynes, including terminal alkyne, were applicable to give C2-alkenylated indoles in 50-99% yield.
Abstract: A unique synthetic utility of a Cp*Co(III) catalyst in comparison with related Cp*Rh(III) catalysts is described. A C2-selective indole alkenylation/annulation sequence proceeded smoothly with catalytic amount of a [Cp*Co(III)(C6H6)](PF6)2 complex and KOAc. Intramolecular addition of an alkenyl-Cp*Co species to a carbamoyl moiety gave pyrroloindolones in 58-89% yield in one pot. Clear difference was observed between the catalytic activity of the Cp*Co(III) complex and those of Cp*Rh(III) complexes, highlighting the unique nucleophilic activity of the organocobalt species. The Cp*Co(III) catalysis was also suitable for simple alkenylation process of N-carbamoyl indoles, and broad range of alkynes, including terminal alkynes, were applicable to give C2-alkenylated indoles in 50-99% yield. Mechanistic studies on C-H activation step under Cp*Co(III) catalysis with the aid of an acetate unit as well as evaluation of the difference between organo-Co(III) species and organo-Rh(III) species are also described.
398 citations
TL;DR: Mechanistic studies revealed the five-membered manganacycle and manganese hydride species as key reaction intermediates in the catalytic cycle, and the redox neutral reaction produces H2 as the major byproduct and eliminates the need for any oxidants, external ligands, or additives.
Abstract: Described herein is a manganese-catalyzed dehydrogenative [4+2] annulation of NH imines and alkynes, a reaction providing highly atom-economical access to diverse isoquinolines. This transformation represents the first example of manganese-catalyzed CH activation of imines; the stoichiometric variant of the cyclomanganation was reported in 1971. The redox neutral reaction produces H2 as the major byproduct and eliminates the need for any oxidants, external ligands, or additives, thus standing out from known isoquinoline synthesis by transition-metal-catalyzed CH activation. Mechanistic studies revealed the five-membered manganacycle and manganese hydride species as key reaction intermediates in the catalytic cycle.
288 citations
TL;DR: Recent progress in cyclization and annulation reactions initiated by ring-opening of small rings is presented, including the own work using donor-acceptor cyclopropanes and cyclobutanes.
215 citations
TL;DR: This is the first asymmetric example in which α-substituted allenoates were utilized as a C4 synthon for phosphine-catalyzed [4+1] annulation.
Abstract: An enantioselective synthesis of spiropyrazolones from allenoate-derived MBH acetates and pyrazolones through a phosphine-mediated [4+1] annulation process has been developed. Spiropyrazolones were readily prepared in good chemical yields and good to high enantioselectivities. This is the first asymmetric example in which α-substituted allenoates were utilized as a C4 synthon for phosphine-catalyzed [4+1] annulation.
205 citations
TL;DR: A convergent, catalytic asymmetric formal [4 + 2] annulation for the synthesis of dihydroquinolones has been developed and simultaneous generation of a reactive aza-o-quinone methide under the basic conditions employed for NHC generation leads to a dual activation approach.
Abstract: A convergent, catalytic asymmetric formal [4 + 2] annulation for the synthesis of dihydroquinolones has been developed. Carboxylic acids can be employed as precursors to NHC enolates through an in situ activation strategy. Simultaneous generation of a reactive aza-o-quinone methide under the basic conditions employed for NHC generation leads to a dual activation approach.
186 citations
TL;DR: The rhodium-catalyzed dearomatizing [3 + 2] annulation reaction of 4-(3-arylpropyl)-1,2,3-triazoles is described, which provides a straightforward synthetic pathway from simple 5-aryl-1-alkynes leading to tricyclic 3,4-fused dihydroindoles via the corresponding 1,2-3-Triazoles.
Abstract: The rhodium-catalyzed dearomatizing [3 + 2] annulation reaction of 4-(3-arylpropyl)-1,2,3-triazoles is described. It provides a straightforward synthetic pathway from simple 5-aryl-1-alkynes leading to tricyclic 3,4-fused dihydroindoles via the corresponding 1,2,3-triazoles.
186 citations
TL;DR: Appropriately substituted 2-alkenylphenols undergo a mild formal [3C+2C] cycloaddition with alkynes when treated with a Rh(III) catalyst and an oxidant.
Abstract: Appropriately substituted 2-alkenylphenols undergo a mild formal [3C+2C] cycloaddition with alkynes when treated with a Rh(III) catalyst and an oxidant. The reaction, which involves the cleavage of the terminal C–H bond of the alkenyl moiety and the dearomatization of the phenol ring, provides a versatile and efficient approach to highly appealing spirocyclic skeletons and occurs with high selectivity.
186 citations
TL;DR: The development of an artificial divergent assembly line generating unprecedented numbers of scaffold variations of terpenoid indole alkaloids is shown, which not only allows practical access to multipotent intermediates, but also enables systematic diversification of skeletal, stereochemical and functional group properties without structural simplification of naturally occurring alkaloid properties.
Abstract: Emulating the biogenesis of natural products, a synthetic strategy is described in which an achiral multipotent intermediate reacts through three distinct [4 + 2] cyclizations and two types of redox-mediated annulation. This results in divergent access to natural product-like scaffolds in 6–9 steps. The efficiency of this approach is highlighted in the total syntheses of three natural products.
169 citations
TL;DR: A convenient and efficient synthetic method has been developed to construct highly functionalized N-bridgehead azepine skeletons, which are of great importance in biological and pharmaceutical industry.
Abstract: A convenient and efficient synthetic method has been developed to construct highly functionalized N-bridgehead azepine skeletons, which are of great importance in biological and pharmaceutical industry. The reaction proceeds through a rhodium(II) azavinyl carbene intermediate, which initiated the intramolecular C-H functionalization with pyrrolyl and indolyl rings. A variety of azepine derivatives were obtained in moderate to good yields under mild reaction conditions with high chemoselectivity. Several interesting derivatizations of the resulting products demonstrate that this method is synthetically valuable and useful.
156 citations
TL;DR: The protocol represents a unique NHC-activation-based approach to access spiro-heterocyclic derivatives bearing a quaternary stereogenic center with high optical purity (up to 95% ee).
Abstract: A highly enantioselective N-heterocyclic carbene (NHC) catalyzed formal [3+2] annulation of α,β-unsaturated aldehydes with azaaurones or aurone generating spiro-heterocycles has been developed. The protocol represents a unique NHC-activation-based approach to access spiro-heterocyclic derivatives bearing a quaternary stereogenic center with high optical purity (up to 95 % ee).
155 citations
TL;DR: A novel and direct approach to synthesize 1-aminoindole derivatives by Rh(iii)-catalyzed cyclization of 2-acetyl-1-arylhydrazines with diazo compounds via aryl C-H activation has been developed that obviates the need of external oxidants and displays a broad substituent scope.
TL;DR: The transformation has demonstrated for the first time that Cu(OAc)2 can be renewable after undergoing an oxidative reaction, and offers a highly efficient approach to the 3-methyleneisoindolin-1-one scaffold.
TL;DR: The red-shifted telluride version of the annulated BODIPY selenide product was found to be sensitive and selective for hypochlorite detection, reversible upon treatment with biothiols.
TL;DR: An efficient, practical, and external-oxidant-free indole synthesis from readily available aryl hydrazines was developed, by using hydrazone as a directing group for Rh(III)-catalyzed C-H activation and alkyne annulation.
Abstract: An efficient, practical, and external-oxidant-free indole synthesis from readily available aryl hydrazines was developed, by using hydrazone as a directing group for RhIII-catalyzed CH activation and alkyne annulation. The hydrazone group was formed by in situ condensation of hydrazines and CO source, whereas its NN bond was served as an internal oxidant, for which we termed it as an auto-formed and auto-cleavable directing group (DGauto). This method needs no step for pre-installation and post-cleavage of the directing group, making it a quite easily scalable approach to access unprotected indoles with high step economy. The DGauto strategy was also applicable for isoquinoline synthesis. In addition, synthetic utilities of this chemistry for rapid assembly of π-extended nitrogen-doped polyheterocycles and bioactive molecules were demonstrated.
TL;DR: A regio- and enantioselective formal [4 + 3] annulation reaction between enals and in situ formed azoalkenes has been achieved, allowing selective access to diverse 1,2-diazepine and pyrazole derivatives from identical substrates.
Abstract: A regio- and enantioselective formal [4 + 3] annulation reaction between enals and in situ formed azoalkenes has been achieved. A diverse set of 1,2-diazepine derivatives were synthesized in good yields with excellent enantioselectivities (often 99% ee). Alternatively, modifying the standard NHC catalyst switched the reactivity toward a formal [4 + 1] annulation to afford functionalized pyrazoles. The electronic and steric properties of the N-heterocyclic carbene organocatalyst play a vital role in controlling the reaction pathway (homoenolate vs acyl-anion reactivity of enal), allowing selective access to diverse 1,2-diazepine and pyrazole derivatives from identical substrates.
TL;DR: In this paper, the authors summarize the annulation reactions via chelation-assisted C−H activation leading to isoquinolines, isoquinolinium salts, or isoquinoline N-oxides.
TL;DR: 1,3-Enynes containing allylic hydrogens cis to the alkyne are shown to act as one- carbon partners, rather than two-carbon partners, in various rhodium-catalyzed oxidative annulations, providing a diverse range of heterocyclic products.
Abstract: 1,3-Enynes containing allylic hydrogens cis to the alkyne are shown to act as one-carbon partners, rather than two-carbon partners, in various rhodium-catalyzed oxidative annulations. The mechanism of these unexpected transformations is proposed to occur through double CH activation, involving a hitherto rare example of the 1,4-migration of a RhIII species. This phenomenon is general across a variety of substrates, and provides a diverse range of heterocyclic products.
TL;DR: A possible mechanism, which involves multiple chelation-assisted ortho C-H activation, alkyne insertion, and reductive elimination, is proposed for this transformation of highly substituted naphthyridine-based polyheteroaromatic compounds.
Abstract: A new method for the synthesis of highly substituted naphthyridine-based polyheteroaromatic compounds in high yields proceeds through rhodium(III)-catalyzed multiple C-H bond cleavage and C-C and C-N bond formation in a one-pot process. Such highly substituted polyheteroaromatic compounds have attracted much attention because of their unique π-conjugation, which make them suitable materials for organic semiconductors and luminescent materials. Furthermore, a possible mechanism, which involves multiple chelation-assisted ortho C-H activation, alkyne insertion, and reductive elimination, is proposed for this transformation.
TL;DR: Vinyl acetate emerges as a convenient acetylene equivalent, facilitating the synthesis of sixteen 3,4-unsubstituted isoquinolones, as well as select heteroaryl-fused pyridones, and the complementary regiochemical preferences of enol ethers versus enol esters/enamides is discussed.
TL;DR: The reaction is proposed to proceed via a directed activation of the olefinic C–H bond followed by two migratory insertions, first across the electron-deficient alkene and then by cyclization back onto the enol moiety.
Abstract: N-Enoxyphthalimides undergo a Rh(III)-catalyzed C–H activation initiated cyclopropanation of electron deficient alkenes. The reaction is proposed to proceed via a directed activation of the olefinic C–H bond followed by two migratory insertions, first across the electron-deficient alkene and then by cyclization back onto the enol moiety. A newly designed isopropylcyclopentadienyl ligand drastically improves yield and diastereoselectivity.
TL;DR: The first example of a dynamic kinetic asymmetric [3 + 2] annulation reaction of aminocyclopropanes with both enol ethers and aldehydes is reported, which gives access to important enantio-enriched nitrogen building blocks for the synthesis of bioactive compounds.
Abstract: We report the first example of a dynamic kinetic asymmetric [3 + 2] annulation reaction of aminocyclopropanes with both enol ethers and aldehydes. Using a Cu catalyst and a commercially available bisoxazoline ligand, cyclopentyl- and tetrahydrofurylamines were obtained in 69-99% yield and up to a 98:2 enantiomeric ratio using the same reaction conditions. The method gives access to important enantio-enriched nitrogen building blocks for the synthesis of bioactive compounds.
TL;DR: An overview of various annulation reactions promoted by metal catalysts including C-H bond functionalization, [2+2-2] cycloaddition, cascade processes, ring closing metathesis, electrophilic aromatization, and various cross-coupling reactions is given.
Abstract: The progress of the metal-catalyzed annulation reactions toward construction of various π-conjugated polycyclic cores with high conjugation extension is described. This article gives a brief overview of various annulation reactions promoted by metal catalysts including C-H bond functionalization, [2+2+2] cycloaddition, cascade processes, ring closing metathesis, electrophilic aromatization, and various cross-coupling reactions. A variety of conjugated polycycles with planar, bowl-shaped, and helical structures have been constructed in high efficiency and selectivity.
TL;DR: A novel and efficient palladium(II)-catalyzed alkenyl C-H activation oxidative annulation of enamides with alkynes for the synthesis of substituted pyrroles has been developed.
TL;DR: Using rhodium-catalyzed sequential oxidative C-H annulation reaction between ketazines and internal alkynes, both N-atoms of the azines could be efficiently incorporated to the desired isoquinolines under very robust and mild reaction conditions.
TL;DR: A diastereoselective (3 + 2) dearomative annulation of 3-substituted indoles with α-haloketones has been developed and significant regiochemical control was observed.
Abstract: A diastereoselective (3 + 2) dearomative annulation of 3-substituted indoles with α-haloketones has been developed. Significant regiochemical control was observed. This methodology provides easy access to highly functionalized cyclopenta- or cyclohexa-fused indoline compounds, which are common structures of many natural products. The synthetic potential of this reaction was demonstrated in the concise syntheses of the core structures of vincorine, isocorymine, and aspidophylline A. DFT studies (B3LYP-D3/6-311++G**/MeOH) on cyclization mechanisms involving the 2-hydroxyallyl cation and its deprotonated oxyallyl cation have been performed. Under the reaction conditions, with a sparingly soluble Na2CO3 base, both species may be present and both pathways are viable. Both pathways support the formation of the experimentally observed O-bound intermediate, its transformation to the final product, the regiochemical and eventual stereochemical outcome of the kinetic cyclization product, and the thermodynamic prefe...
TL;DR: In this article, a dinuclear (electron-deficient η5-cyclopentadienyl) rhodium(III) complex was synthesized on a preparative scale via the cyclotrimerization of silylacetylenes and two alkynyl esters.
Abstract: A dinuclear (electron-deficient η5-cyclopentadienyl)rhodium(III) complex was synthesized on a preparative scale via the rhodium-catalyzed cross [2+2+1] cyclotrimerization of silylacetylenes and two alkynyl esters, leading to substituted silylfulvenes, followed by reductive complexation with rhodium(III) chloride in ethanol. The thus obtained dinuclear (electron-deficient η5-cyclopentadienyl)rhodium(III) complex is a highly active precatalyst for the oxidative annulation of anilides with internal alkynes under ambient conditions (at room temperature under air). A preference for annulation across electron-rich substrates over electron-deficient substrates was observed using this electron-deficient rhodium(III) complex.
TL;DR: A sterically hindered homoenolate has been generated by the NHC-catalyzed conjugate umpolung of β,β-disubstituted enals and successfully employed in a facile stereoselective annulation with isatins.
Abstract: A sterically hindered homoenolate has been generated by the NHC-catalyzed conjugate umpolung of β,β-disubstituted enals and successfully employed in a facile stereoselective annulation with isatins. The strategy provides efficient access to spirocyclic oxindoles bearing two highly congested contiguous quaternary carbon centers. The use of a Bronsted acid cocatalyst was found to be crucial for guaranteeing both excellent reactivity and high stereoselectivity.
TL;DR: A fast and simple divergent synthesis of multisubstituted quinazolines and benzimidazoles was developed from readily available amidines, via iodine(III)-promoted oxidative C(sp(3)C-H/sp(2)H-H direct coupling of the amidine with K2S2O8 as the oxidant.
TL;DR: A practical and efficient Rh(III)-catalyzed aerobic C-H activation has been developed for the facile synthesis of a broad range of indoles from simple anilines and alkynes.
TL;DR: A transition-metal-free method for the synthesis of C6 phenanthridine derivatives by arylative cyclization of 2-isocyanobiphenyls with arylamines in one pot was developed.