Showing papers on "Annulation published in 2021"
TL;DR: The photo-electrocatalytic functionalization of quinoxalin-2(1H)-ones has emerged as a promising and powerful approach for post-synthetic modification.
85 citations
TL;DR: In this paper, the rhodium(III)-catalyzed C-H activation of anilines bearing an N-isoquinolyl directing group for oxidative [3+2] annulation with four classes of internal alkynes, leading to atroposelective indole synthesis via dynamic kinetic annulation.
Abstract: Reported herein is the rhodium(III)-catalyzed C-H activation of anilines bearing an N-isoquinolyl directing group for oxidative [3+2] annulation with four classes of internal alkynes, leading to atroposelective indole synthesis via dynamic kinetic annulation with C-N reductive elimination constituting the stereo-determining step. This reaction proceeds under mild conditions with high regio- and enantioselectivity and functional group compatibility.
71 citations
TL;DR: In this paper, a Ru(II)-catalyzed enanti-selective C-H activation/annulation of sulfoximines with α-carbonyl sulfoxonium ylides using a novel class of chiral binaphthyl monocarboxylic acids as chiral ligands was described.
Abstract: Ru(II)-catalyzed enantioselective C-H functionalization involving an enantiodetermining C-H cleavage step remains undeveloped. Here we describe a Ru(II)-catalyzed enantioselective C-H activation/annulation of sulfoximines with α-carbonyl sulfoxonium ylides using a novel class of chiral binaphthyl monocarboxylic acids as chiral ligands, which can be easily and modularly prepared from 1,1'-binaphthyl-2,2'-dicarboxylic acid. A broad range of sulfur-stereogenic sulfoximines were prepared in high yields with excellent enantioselectivities (up to 99% yield and 99% ee) via desymmetrization, kinetic resolution, and parallel kinetic resolution. Furthermore, the resolution products can be easily transformed to chiral sulfoxides and key intermediates for kinase inhibitors.
71 citations
TL;DR: In this paper, an enantio- and diastereodivergent synthesis of rigid spirocycles through dual-metal-catalyzed [3+2] annulation of oxy π-allyl metallic dipoles with less commonly employed nucleophilic dipoles (imino esters) was reported.
Abstract: The development of efficient and straightforward methods for obtaining all optically active isomers of structurally rigid spirocycles from readily available starting materials is of great value in drug discovery and chiral ligand development. However, the stereodivergent synthesis of spirocycles bearing multiple stereocenters remains an unsolved challenge owing to steric hindrance and ring strain. Herein, we report an enantio- and diastereodivergent synthesis of rigid spirocycles through dual-metal-catalyzed [3+2] annulation of oxy π-allyl metallic dipoles with less commonly employed nucleophilic dipoles (imino esters). A series of spiro compounds bearing a pyrroline and an olefin were easily synthesized in an enantio- and diastereodivergent manner (up to 19:1 dr, >99 % ee), which showed great promise as a new type of N-olefin ligand. Preliminary mechanistic studies were also carried out to understand the process of this bimetallic catalysis.
70 citations
TL;DR: In this paper, a rhodium(III)-catalyzed enantioselective C-H activation/annulation process is disclosed. But it is not shown how to obtain a chiral azoniahelicenes with high yields and enanti-selectivity.
Abstract: A rhodium(III)-catalyzed enantioselective C-H activation/annulation process is disclosed. With a catalyst derived from a chiral CpRh(III) complex and a chiral acid, the direct annulation reactions between 1-aryl isoquinoline derivatives and alkynes take place smoothly to afford a series of chiral azoniahelicenes in excellent yields and enantioselectivity (up to 99% yield and 96% ee). Mechanistic studies suggest that C-H bond cleavage may be the turnover-limiting step.
64 citations
TL;DR: In this paper, a catalytic atroposelective cycloaddition reaction between thioureas and ynals was developed for axially chiral thiazine derivative products.
Abstract: A catalytic atroposelective cycloaddition reaction between thioureas and ynals is developed. This reaction features the first NHC-catalyzed addition of thioureas to acetylenic acylazolium intermediates to eventually set up C-N axial chirality with excellent optical purities. The obtained axially chiral thiazine derivative products bear multiple functional groups and are feasible for further transformations.
60 citations
TL;DR: Ring-opening transformations of donor-acceptor cyclopropanes (DAC) with carbon-centered nucleophiles is a simple, straight-forward approach to 1,3-bifunctional compounds that has witnessed remarkable progress over the past several years.
Abstract: Ring-opening transformations of donor–acceptor cyclopropanes (DAC) with carbon-centered nucleophiles is a simple, straight-forward approach to 1,3-bifunctional compounds that has witnessed remarkable progress over the past several years. To date, different reactivity patterns of DACs have been successfully exploited in racemic/stereoselective syntheses of various acyclic compounds or carbocycles with an impressive structural diversity. The thriving strategies have been successfully utilized in multistep synthesis of complex target molecules. Herein, the recent advances (2015–present) in the ring-opening of DAC involving electron rich arenes and indoles, active methylene compounds, various dipolarophiles, organoborates/boronates, vinyl ethers etc. following Friedel–Crafts alkylation, annulation/formal cycloaddition reaction, organocatalytic reaction, Nazarov cyclisation etc. are presented.
54 citations
TL;DR: A cooperative N-heterocyclic carbene (NHC)/iridium catalysis was developed to achieve highly stereoselective and regiodivergent [3+2] and [3 + 3] annulation reactions of 2-indolyl allyl carbine as discussed by the authors.
Abstract: A cooperative N-heterocyclic carbene (NHC)/iridium catalysis has been developed to achieve highly stereoselective and regiodivergent [3 + 2] and [3 + 3] annulation reactions of 2-indolyl allyl carb...
50 citations
TL;DR: This review will provide an introduction to transition metal-catalyzed C-H activation for the synthesis of polycycles, helping researchers to discover indirect connections and reveal hidden opportunities, and promote the discovery of novel synthetic strategies relying on C- H activation.
Abstract: Polycycles are abundantly present in numerous advanced chemicals, functional materials, bioactive molecules and natural products. However, the strategies for the synthesis of polycycles are limited to classical reactions and transition metal-catalyzed cross-coupling reactions, requiring pre-functionalized starting materials and lengthy synthetic operations. The emergence of novel approaches shows great promise for the fields of organic/medicinal/materials chemistry. Among them, transition metal-catalyzed C-H activation followed by intermolecular annulation reactions prevail, due to their straightforward manner with high atom- and step-economy, providing rapid, concise and efficient methods for the construction of diverse polycycles. Several strategies have been developed for the synthesis of polycycles, relying on sequential multiple C-H activation/annulation, or combination of C-H activation/annulation and further interaction with a proximal group, or merger of C-H activation with a cycloaddition reaction, or in situ formation of the directing group. These are attractive, efficient, step- and atom-economic methods starting from commercially available materials. This Minireview will provide an introduction to transition metal-catalyzed C-H activation for the synthesis of polycycles, helping researchers to discover indirect connections and reveal hidden opportunities. It will also promote the discovery of novel synthetic strategies relying on C-H activation.
46 citations
TL;DR: A cobalt-promoted electrochemical 1,2-diarylation of alkenes with electron-rich aromatic hydrocarbons via direct dual C-H functionalizations is described, which employs a radical relay strategy to produce polyaryl-functionalized alkanes.
Abstract: A cobalt-promoted electrochemical 1,2-diarylation of alkenes with electron-rich aromatic hydrocarbons via direct dual C-H functionalizations is described, which employs a radical relay strategy to produce polyaryl-functionalized alkanes. Simply by using graphite rod cathode instead of platinum plate cathode, chemoselectivity of this radical relay strategy is shifted to the dehydrogenative [2+2+2] cycloaddition via 1,2-diarylation, annulation, and dehydrogenation cascades leading to complex 11,12-dihydroindolo[2,3-a]carbazoles. Mechanistical studies indicate that a key step for the radical relay processes is transformations of the aromatic hydrocarbons to the aryl sp2 -hybridized carbon-centered radicals via deprotonation of the corresponding aryl radical cation intermediates with bases.
46 citations
TL;DR: In this paper, the first electrochemical metal-catalyzed cycloadditions to assemble valuable seven-membered benzoxepine skeletons by C-H/O-H activation were described.
Abstract: Electrooxidative annulations involving mild transition metal-catalyzed C-H activation have emerged as a transformative strategy for the rapid construction of five- and six-membered heterocycles. In contrast, we herein describe the first electrochemical metal-catalyzed [5+2] cycloadditions to assemble valuable seven-membered benzoxepine skeletons by C-H/O-H activation. The efficient alkyne annulation featured ample substrate scope, using electricity as the only oxidant. Mechanistic studies provided strong support for a rhodium(III/I) regime, involving a benzoxepine-coordinated rhodium(I) sandwich complex as the catalyst resting state, which was re-oxidized to rhodium(III) by anodic oxidation.
TL;DR: The isolation of key intermediates and detailed mechanistic studies, including unprecedented cyclovoltammetric analysis of a seven‐membered ruthenacycle, provided support for an unusual ruthensium(II/III/I) regime.
Abstract: The electrochemical three-component assembly of isoquinolines has been accomplished by ruthenaelectro-catalyzed C-H/N-H functionalization. The robustness of the electrocatalysis was reflected by an ample substrate scope, an efficient electrooxidation, and an operationally friendly procedure. The isolation of key intermediates and detailed mechanistic studies, including unprecedented cyclovoltammetric analysis of a seven-membered ruthenacycle, provided support for an unusual ruthenium(II/III/I) regime.
TL;DR: In this paper, a review highlights representative advances in organic synthesis based on zwitterionic π-allyl palladium and propargyl palladium, which includes both structural scaffolds used in the pharmaceutical industry and novel heterocyclic skeletons with potential biological appeal.
Abstract: In the past few years, Pd-catalyzed annulation reactions through zwitterionic π-allyl palladium intermediates have been extensively investigated. Meanwhile, zwitterionic π-allyl palladium and propargyl palladium have also been successfully demonstrated to be a vital and versatile synthon for the construction of carbocyclic and heterocyclic compounds, which include both structural scaffolds used in the pharmaceutical industry and novel heterocyclic skeletons with potential biological appeal. This review highlights representative advances in organic synthesis based on zwitterionic π-allyl palladium and propargyl palladium.
TL;DR: In this paper, an asymmetric annulation of arylnitrones with different classes of alkynes catalyzed by chiral rhodium(III) complexes, with the nitrone acting as an electrophilic directing group, was reported.
Abstract: Reported herein is asymmetric [3+2] annulation of arylnitrones with different classes of alkynes catalyzed by chiral rhodium(III) complexes, with the nitrone acting as an electrophilic directing group. Three classes of chiral indenes/indenones have been effectively constructed, depending on the nature of the substrates. The coupling system features mild reaction conditions, excellent enantioselectivity, and high atom-economy. In particular, the coupling of N-benzylnitrones and different classes of sterically hindered alkynes afforded C-C or C-N atropochiral pentatomic biaryls with a C-centered point-chirality in excellent enantio- and diastereoselectivity (45 examples, average 95.6 % ee). These chiral center and axis are disposed in a distal fashion and they are constructed via two distinct migratory insertions that are stereo-determining and are under catalyst control.
TL;DR: In this paper, the first application of 2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile (4CzIPN) as a photocatalyst for the synthesis of spiroγ-lactam derivatives, in which the use of transition metals and a high reaction temperature could be avoided.
Abstract: Photocatalytic strategies for the preparation of 3-phosphoryl/trifluoromethyl/thiocyanato azaspiro[4.5]trienones via a radical-initiated cascade annulation reaction of N-arylpropiolamides with phosphorus reagents, 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (Togni's reagent II) or NH4SCN have been developed under blue LED irradiation at room temperature. The novel synthetic methodologies constitute the first application of 2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile (4CzIPN) as a photocatalyst for the synthesis of spiro-γ-lactam derivatives, in which the use of transition metals and a high reaction temperature could be avoided. The reactions are operationally simple, easy to scale up, and metal-free with wide reaction scope and good functional group tolerance.
TL;DR: In this paper, a ruthenium(II)-catalyzed C-C/C-N annulation of 2-arylquinazolinones with vinylene carbonate is reported to synthesize fused quinazolinone.
TL;DR: In this article, the additive controlled divergent synthesis of tetrasubstituted 1,3-enynes and alkynylated 3H-pyrrolo[1,2-a]indol-3-ones through rhodium-catalyzed C-H alkenylation/DG migration and annulation was reported.
17 Sep 2021
TL;DR: An atroposelectively diversity-oriented synthetic strategy was developed for the divergent synthesis of axially chiral heterocycles through organocatalytic asymmetric intramolecular annulation of a polyene-like substance.
Abstract: An atroposelectively diversity-oriented synthetic strategy was developed for the divergent synthesis of axially chiral heterocycles through organocatalytic asymmetric intramolecular annulation of a...
TL;DR: In this article, a vinyl thianthrenium salt was introduced as an effective vinylating reagent, which can be readily prepared from ethylene gas at atmospheric pressure in one step and is broadly useful in the annulation chemistry of (hetero)cycles, N-vinylation of heterocyclic compounds, and palladium-catalyzed crosscoupling reactions.
Abstract: The use of vinyl electrophiles in synthesis has been hampered by the lack of access to a suitable reagent that is practical and of appropriate reactivity. In this work we introduce a vinyl thianthrenium salt as an effective vinylating reagent. The bench-stable, crystalline reagent can be readily prepared from ethylene gas at atmospheric pressure in one step and is broadly useful in the annulation chemistry of (hetero)cycles, N-vinylation of heterocyclic compounds, and palladium-catalyzed cross-coupling reactions. The structural features of the thianthrene core enable a distinct synthesis and reactivity profile, unprecedented for other vinyl sulfonium derivatives.
TL;DR: In this article, the synthesis of NH-free pyrroles via Pd-catalyzed annulation of enaminones and alkenes is reported, and the interesting evolution of hydrogen gas from the reactions has been observed by a hydrogen detector.
TL;DR: In this paper, a scandium-catalyzed asymmetric dearomative spiro-annulation of quinolines with alkynes was reported, leading to efficient and selective construction of spiro molecular architectures that were previously difficult to access by other means.
Abstract: The catalytic enantioselective construction of three-dimensional molecular architectures from planar aromatics such as quinolines is of great interest and importance from the viewpoint of both organic synthesis and drug discovery, but there still exist many challenges. Here, we report the scandium-catalyzed asymmetric dearomative spiro-annulation of quinolines with alkynes. This protocol offers an efficient and selective route for the synthesis of spiro-dihydroquinoline derivatives containing a quaternary carbon stereocenter with an unprotected N-H group from readily accessible quinolines and diverse alkynes, featuring high yields, high enantioselectivity, 100% atom-efficiency, and broad substrate scope. Experimental and density functional theory studies revealed that the reaction proceeded through the C-H activation of the 2-aryl substituent in a quinoline substrate by a scandium alkyl (or amido) species followed by alkyne insertion into the Sc-aryl bond and the subsequent dearomative 1,2-addition of the resulting scandium alkenyl species to the C═N unit in the quinoline moiety. This work opens a new avenue for the dearomatization of quinolines, leading to efficient and selective construction of spiro molecular architectures that were previously difficult to access by other means.
TL;DR: In this paper, a rhodium(III)-catalyzed formal C-H [5 + 1] cyclization of 2-pyrrolyl/indolylanilines with vinylene carbonate has been explored towards the potent assembly of diverse 4-methylpyrrolo[1,2-a]quinoxalines.
Abstract: A rhodium(III)-catalyzed formal C–H [5 + 1] cyclization of 2-pyrrolyl/indolylanilines with vinylene carbonate has been explored towards the potent assembly of diverse 4-methylpyrrolo[1,2-a]quinoxalines. This established protocol is characterized by an exceedingly simple reaction system, and excellent functional group toleration and yields. Most importantly, entirely distinct from documented [4 + 2] cyclization conversions, herein, the emerging vinylene carbonate firstly presents as a C1 synthon to realize [5 + 1] annulation and shows new chemical reactivity. Biological studies indicate that these prepared products are promising candidates in terms of their antibacterial activity.
TL;DR: In this paper, an electrochemical vinylic C-H annulation of acrylamides with alkynes has been reported, which can yield cyclic products in good to excellent yield.
Abstract: α-Pyridones and α-pyrones are ubiquitous structural motifs found in natural products and biologically active small molecules Here, we report an Rh-catalyzed electrochemical vinylic C-H annulation of acrylamides with alkynes, affording cyclic products in good to excellent yield Divergent syntheses of α-pyridones and cyclic imidates are accomplished by employing N-phenyl acrylamides and N-tosyl acrylamides as substrates, respectively Additionally, excellent regioselectivities are achieved when using unsymmetrical alkynes This electrochemical process is environmentally benign compared to traditional transition metal-catalyzed C-H annulations because it avoids the use of stoichiometric metal oxidants DFT calculations elucidated the reaction mechanism and origins of substituent-controlled chemoselectivity The sequential C-H activation and alkyne insertion under rhodium catalysis leads to the seven-membered ring vinyl-rhodium intermediate This intermediate undergoes either the classic neutral concerted reductive elimination to produce α-pyridones, or the ionic stepwise pathway to produce cyclic imidates
TL;DR: In this paper, an NHC-catalyzed atroposelective reaction between ynals and urazoles is disclosed, which allows efficient access to axially chiral and heteroatom-rich urazole derivatives with potential applications in bioactive molecules and catalysis.
TL;DR: In this paper, a transition metal catalyzed denitrogenative annulation reaction of 1,2,3-triazoles via a metal carbene intermediate has been shown to enable the construction of nitrogen-rich molecules.
Abstract: ConspectusThe pursuit for the discovery of new and powerful synthetic methods to access high-value N-heterocycles has been at the forefront of organic chemistry research for more than a century. Considering the importance of N-scaffolds in modern science, over the past few decades, great research efforts have been made to develop efficient synthetic methods for the construction of nitrogen-rich molecules. Among many efforts, transition metal catalyzed denitrogenative annulation reaction has emerged as a cornerstone due to its innate versatility and wider scope of application.The denitrogenative annulation approach offers clear advantages over many existing methods, as it enables effective, single-step interconversion of easily available feedstocks into a variety of other important N-containing heterocyclic frameworks. Recently, transition metal catalyzed denitrogenative annulation reaction of the 1,2,3-triazole via a metal carbene intermediate sparked significant interest in the application of various important heterocycle syntheses. Denitrogenative annulation reaction of 1,2,3-triazoles proceeds via an ionic mechanism. Recently, we demonstrated a new concept for the denitrogenative reaction of triazoles with alkenes and alkynes via in situ generated 2-(diazomethyl)pyridines. The method takes advantage of the inherent properties of a Co(III)-carbene radical intermediate and is the first report of the denitrogenative annulation/cyclopropanation by a radical-activation mechanism.On the other hand, in contrast to the denitrogenative annulation of 1,2,3-triazole, annulation reaction of 1,2,3,4-tetrazole (a surrogate of azide having an important pyridyl unit) via metal nitrene remains a big challenge. Previously, flash vacuum pyrolysis studies had been used for nitrene-nitrene rearrangement of 1,2,3,4-tetrazole at high temperature. This Account summarizes our recent efforts in developing transition metal catalyzed denitrogenative annulation of 1,2,3-triazoles via a radical mechanism and 1,2,3,4-tetrazoles via metal nitrene to access important nitrogen-rich molecules. We demonstrated that the 1,2,3,4-tetrazole under Ir-catalyzed reaction conditions can produce a productive Ir-nitrene intermediate that can successfully be employed for the construction of a wide number of α-carbolines and 7-azaindoles. Moreover, we developed an iron-based unique strategy for the intermolecular denitrogenative annulation reaction between tetrazoles and alkynes. The reaction overcomes the traditional click reaction and proceeds via an unprecedented metalloradical activation mechanism. Furthermore, we used our understanding of tetrazole reactivity to design an iron-catalyzed intramolecular denitrogenative C(sp3)-H amination reaction of primary, secondary, and tertiary centers by using a metalloradical activation concept. At the same time, we also developed a general catalytic method to enable two distinct reactions (1,3-cycloaddition and denitrogenative annulation) using Mn(TPP)Cl that afforded two different classes of nitrogen heterocycles. Mechanistic studies showed that although the click reaction likely proceeds through an ionic mechanism and the denitrogenative annulation reaction likely proceeds via an electrophilic metallonitrene intermediate rather than a metallonitrene radical intermediate. Finally, we report an iron-catalyzed rearrangement reaction (ring expansion/migration) that proceeded with an unprecedented level of selectivity, reactivity, and functional group tolerance offering rapid access to numerous complex N-heterocycles. We believe that our continuous efforts in this field would be beneficial for pharmaceutical industries, drug discovery, and other fields of medicinal chemistry.
TL;DR: In this paper, an efficient three-component tandem reaction of polyfluoroalkyl peroxides with sulfinates for the facile construction of fluoro-alkylated tetrasubstituted furan derivatives has been developed.
TL;DR: In this paper, the authors summarize the recent research on the Rh-catalyzed cascade arene C-H bond activation/annulation toward diverse heterocyclic compounds.
Abstract: The Rh-catalyzed C–H bond activation/annulation provides a new strategy for the synthesis of new frameworks In this review, we summarize the recent research on the Rh-catalyzed cascade arene C–H bond activation/annulation toward diverse heterocyclic compounds The application, scope, limitations and mechanism of these transformations are also discussed
TL;DR: In this article, a transition-metal-free one-pot three-component annulation between diaryliodonium triflates, cyclic and acyclic aliphatic amines, and carbon disulfide is developed.