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Palladium‐Catalyzed Cascade Annulation To Construct Functionalized β‐ and γ‐Lactones in Ionic Liquids
Angewandte Chemie International Edition
Abstract
A highly efficient and mild palladium-catalyzed, one-pot, four-step cascade annulation has been developed to afford functionalized beta- and gamma-lactones in moderate to good yields with high regio- and diastereoselectivities in ionic liquids. The employment of ionic liquids under mild reaction conditions makes this transformation green and practical. Especially, this reaction provided a novel and convenient methodology for the construction of naturally occurring biologically active beta- and gamma-lactones.
... The proposed mechanism suggested that the reaction involved two catalytic cycles separated temporarily. Firstly, cyclative alkynylation occurred, generating 3-alkynylindoles (196); then, a subsequent aminopalladation afforded 2,3 -bisindoles. It is worth noting that the charcoal-supported catalyst was the product of the cyclization of 3-alkynylindoles (196) to the desired bisindoles (195) (Scheme 58). ...
... Firstly, cyclative alkynylation occurred, generating 3-alkynylindoles (196); then, a subsequent aminopalladation afforded 2,3 -bisindoles. It is worth noting that the charcoal-supported catalyst was the product of the cyclization of 3-alkynylindoles (196) to the desired bisindoles (195) (Scheme 58). This methodology was a rare case using Pd/C as pre-catalyst for oxidative Pd II -catalyzed transformations [189]. ...
... The pro mechanism suggested that the reaction involved two catalytic cycles separated temp ily. Firstly, cyclative alkynylation occurred, generating 3-alkynylindoles (196); then, sequent aminopalladation afforded 2,3′-bisindoles. It is worth noting that the cha supported catalyst was the product of the cyclization of 3-alkynylindoles (196) to th sired bisindoles (195) (Scheme 58). ...
As part of natural products or biologically active compounds, the synthesis of nitrogen-containing heterocycles is becoming incredibly valuable. Palladium is a transition metal that is widely utilized as a catalyst to facilitate carbon-carbon and carbon-heteroatom coupling; it is used in the synthesis of various heterocycles. This review includes the twelve years of successful indole synthesis using various palladium catalysts to establish carbon-carbon or carbon-nitrogen coupling, as well as the conditions that have been optimized.
... Synthesis of b-lactone derivatives (1027, Scheme 444) via onepot cascade annulation of alkynoate (1025) with but-3-enoic acid (1026) catalyzed by palladium chloride (PdCl 2 ) and silver nitrate (AgNO 3 ) has been achieved by Jiang and co-workers in 1-ethyl hydroxyl-3-methylimidazolium chloride [C 2 OHmim][Cl] and acetonitrile (5:1) at rt for 12-24 h [623]. The ILs promoted the activation of Pd catalysts which promoted trans-chloropalladation of 1025 to get vinyl palladium, followed by insertion of 1026 and reductive elimination to yield 1027. ...
Heterocycles constitute the integral part of the most of United States food and drug administration (USFDA) approved drugs. Over the past decade, ionic liquids have emerged as a clean, efficient and environmentally benign alternative to the hazardous volatile organic solvents in addition to numerous other remarkable applications owing to their renewability, biodegradability, abundance and inexpensive nature. These properties could be finely tuned based on the demand of several applications in chemical transformations through alteration of their compositional counterparts such as; anions and cations. The current work emphasizes the significant insights into the undisputable applications of these ionic liquids such as catalyst, solvent, co-solvent, ligand in homo and heterogeneous reactions and their use as support in several synthetic transformations. Significant efforts have been made to provide critical inputs on the mechanistic insights such as hydrogen bond formation, amphiphilic electrophile-nucleophile dual activation, bifunctional catalysis, phase-transfer catalysis, and organocatalysis for ionic liquid catalyzed organic transformation. Additionally, the present comprehensive and critical review shall help the reader to select the suitable ILs for synthesizing of desired heterocycles. The present review shall focus on recent advancements and applications of ionic liquids as solvent and catalysts in the synthesis of heterocycles reported from 2013 to 2020.
... [26,27] Since the discovery of metal-catalyzed cross-coupling reactions, [28] haloalkenes and 1,2-dihaloalkenes are extensively utilized in the construction of geometrically defined alkenes. [29][30][31][32] Moreover, alkenyl halides are included in many biologically active compounds, such as pharmaceuticals [33] or agrochemicals. [34] On the other hand, imidoyl halides (aza-analogs of acyl halides) are intermediates widely utilized in the synthesis of nitrogen-containing compounds. ...
N‐Alkenyl compounds are versatile synthetic building blocks and their stereoselective transformations are key processes in the synthesis of many prominent classes of natural products, pharmaceuticals, and agrochemicals. However, a large structural variety of known N‐alkenyl compounds and their diverse reactivity have so far precluded the development of a general method for their stereoselective synthesis. Herein we present an aluminum halide‐mediated, highly stereoselective, efficient and scalable transformation of commercially available N‐fluoroalkyl‐1,2,3‐triazoles to N‐haloalkenyl imidoyl halides, and demonstrate their use in the synthesis of stereodefined N‐alkenyl amides, amidines, imines, hydrazonoamides, imidothioates, iminophosphonates, 1,2,4‐triazoles and tetrazoles. The reaction is of wide scope on both the triazole substrate and aluminum halide, providing highly functionalized products. Mechanistic and computational investigations suggest a reaction mechanism involving the triazole ring opening, initiated by the coordination of nitrogen one of the triazole ring to the Lewis acid, N2 elimination and the formation of a vinyl cation intermediate, which reacts with nitrogen‐bound aluminum halide, followed by a series of halide exchange reactions on C−X and Al−X bonds.
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... 15 For example, dihaloalkenes containing two different halogens could undergo cross-coupling reactions in a step-wise manner for the installment of two different molecular fragments. 7,[16][17][18][19][20][21][22][23][24][25][26][27] In this regard, significant efforts have been devoted to the construction of dihaloalkenes. However, the regio-and stereoselective, yet environmentally friendly synthesis of dihaloalkenes with a broad scope is still challenging. ...
We describe a catalyst-free 1,2-trans-dihalogenation of alkynes with an unprecedented substrate scope and exclusive regio- and stereoselectivity. This versatile dihalogenation system—a combination of NX¹S electrophile and alkali metal halide (MX²) in acetic acid—is applicable for diverse categories of alkynes (electron-rich or poor alkynes, internal and terminal alkynes, or heteroatoms such as O-, N-, S-substituted alkynes). The hydrogen bonding donor solvent acetic acid is essential for the in-situ generation of X¹X² electrophile, including ICl, IBr, BrCl, I2, and Br2.
An unprecedented acid‐promoted skeletal reorganization process of pull–pull alkylidenecyclobutanes is discovered. This transformation provides an efficient synthetic route to functionalized three‐substituted γ‐butyrolactones in moderate‐to‐high yields. image © 2025 WILEY‐VCH GmbH
A palladium‐catalyzed divergent cascade annulation reaction of unactivated cycloalkenes with alkynoic acids under aerobic conditions is accomplished. This catalytic protocol provides an efficient and economical strategy to accommodate a broad scope of (E)‐γ‐lactones fused five‐ or six‐membered ring motifs with good regioselectivities and yields (57 examples, up to 94 % yield and E/Z up to 98 : 2). More importantly, the developed catalytic strategy is applicable to a wide array of unactivated cycloalkenes, including cyclopentene, cyclohexa‐1,3‐diene, cyclohexa‐1,4‐diene, cyclohepta‐1,3‐diene and conjugated 1,3‐diene.
An efficient and reliable NHC‐palladium‐catalyzed cascade decarboxylative coupling of alkynoic acids with 2‐alkynylanilines for the rapid and straightforward assembly of synthetically valuable 3‐alkynylindole derivatives in eco‐friendly medium is described. Control experiments revealed that NHC−Pd catalysts and base were all essential for this catalytic system. More importantly, this approach features mild reaction conditions, excellent functional group compatibility, and reasonable to excellent yields.
A palladium-catalyzed amination oxidation of electron-rich olefins with anilines under air atmosphere at room temperature in ionic liquids was accomplished. Herein, H2O2 serves as the oxidant and the oxygen source...
An N‐heterocyclic carbene palladium (NHC‐palladium)‐catalyzed denitrogenative coupling of aryldiazonium salts with terminal alkynes in ionic liquids has been accomplished. This catalytic strategy provides an effective and green synthetic protocol for the assembly of structurally diverse internal alkynes with excellent functional group compatibility and mild conditions. In the presence of 1 mol % of IMes‐Pd‐Im‐Cl2 as the catalyst, a wide range of terminal alkynes and aryldiazonium salts could be excellently tolerated. Basic ionic liquid plays a crucial role in this catalytic system, which not only acts as the green solvent, but also provides basic environment for the carbon‐carbon bond formation process. Notably, this catalytic system could be recycled up to six times and reused without significant loss of catalytic activity.
Pd-catalyzed regioselective amination of unactivated alkene remains a challenge and is of great interest. Herein, a palladium-catalyzed and ligand-controlled strategy for the Markovnikov selective oxidative amination of 4-pentenoic acid has...
Herein, a palladium-catalyzed 1,1-aminoxylation of 3-butenoic acid and 2-alkynylanilines has been developed, achieving the installation of two distinct heteroatom motifs across an olefin skeleton. The strategy features a high step...
A palladium‐catalyzed cascade cyclization/alkenylation for the assembly of synthetically valuable isoxazolyl vinylsilane derivative has been accomplished. Easily accessible ynone oximes, and available vinylsilane agents were used as the reaction starting materials This protocol features broad substrate scope, good functional group tolerance, and good step‐ and atom‐economy. Remarkably, this approach provides a new approach for the construction of structurally diverse isoxazolyl‐containing vinylsilanes with high molecular complexity, showing a promising application in synthetic and pharmaceutical chemistry.
A novel and reliable palladium‐catalyzed oxylallylation of alkynone oxime ethers with fluorine‐containing alkenes was accomplished. Using the bulk industrial chemical 3‐bromo‐3,3‐difluoroprop‐1‐ene as the coupling partner, this synthetic methodology offers the first example for the assembly of structurally diverse gem‐difluorinated isoxazole derivatives in moderate to good yields with high atom‐ and step‐economy and excellent functional group compatibility. More importantly, this strategy allows for the direct combination of the isoxazole motifs and gem‐difluoroalkene unit, which is not easy to obtain through a general synthetic strategy.
Ionic liquid (IL) catalysed organic syntheses have emerged as a great approach to improve synthetic productivity. Particularly IL catalyzed domino reactions enable the synthesis of organic compounds with high regio/stereoselectivity from simple starting materials. Being the designer solvents, IL promoted domino reactions lead to the eco-friendly green synthetic steps with high-percentage yield. In this review, we have summarized the IL catalyzed one pot tandem reactions for the synthesis of highly functionalized organic molecules. The reaction mechanisms, regioselectivity, and stereoselectivity of the reactions are described in detail. This review has been summarized to extend the synthetic applications of IL catalyzed domino reactions in future.
A metal-controlled divergent protocol for the synthesis of α- and β-substituted γ-butyrolactones was developed through intramolecular coupling of epoxides with alcohols. This method provides an efficient and practicable way to afford γ-butyrolactones with good efficiency, excellent regioselectivity, and broad substrate scope.
Herein, the PdII‐catalyzed construction of functionalized dihaloalkenynes from haloalkynes via a self‐haloalkynylation reaction, without specialized ligands or oxidizing additives, is reported. The method tolerates a diverse range of haloalkynes, including electron‐donating and electron‐withdrawing functional groups, such as macrocyclic alkynols, spiro‐oxy ring alkynols, and even carbazole‐containing, pyrrolidine‐2,5‐dione‐containing and silyl‐protected bromoalkynes. Using an opposite lithium halide (LiX) to the haloalkyne starting material, remarkably high regio‐ and stereoselectivity of the haloalkynylation reaction is possible, yielding 1‐bromo‐2‐chloroalkenyne or 2‐bromo‐1‐chloroalkenyne products as desired.
An N‐heterocyclic carbene palladium (NHC‐palladium)‐catalyzed cascade annulation of alkynoic acids with unactivated alkenes under an oxygen atmosphere in ionic liquids is described. This protocol enables facile access for the preparation of diverse alkyl substituted α‐methylene‐γ‐lactones in moderate to good yields with excellent Z/E selectivity. Moreover, the ionic liquid not only acts as the green solvent, but also as the eco‐friendly chlorine source, thus avoiding the use of excess metal halides such as cupric chloride. Some preliminary mechanistic studies were performed, which further revealed possible pathways for this cascade annulation.
A novel and expedient cascade strategy has been demonstrated for the synthesis of fused benzo‐aza‐oxa‐[5‐6‐5] tetracycles in high yields and diastereoselectivities (up to 20 : 1 dr). The strategy was fulfilled through palladium‐catalyzed oxidative convergent assembly of functionally divergent anilines and 3‐butenoic acid with five chemical bonds constructed. Coupled with control experiments and deuterium labelled studies, DFT calculations were performed for the proposed mechanism. The utility of the illustrated strategy is emphasized by gram‐scale syntheses, late‐stage functionalization, and the transformation to a key core of natural products such as martinellic acid and seneciobipyrrolidine.
A novel and expedient cascade strategy has been demonstrated for the advanced synthesis of fused benzo‐azaoxa‐[5‐6‐5] tetracycles in high yields and diastereoselectivities (up to 20:1 dr). The strategy was fulfilled through palladium‐catalyzed oxidative convergent assembly of functionally divergent anilines and 3‐butenoic acid with five chemical bonds constructed. Coupled with control experiments and deuterium labelled studies, DFT calculations were performed for the proposed mechanism. The utility of the illustrated strategy is emphasized by gram‐scale syntheses, late‐stage functionalization, and the transformation to a key core of natural products such as martinellic acid and incargranine B.
We have developed a hydrogen bond network-assisted highly regio and stereoselective (radio)dihalogenation of alkynes and alkenes using two nucleophilic alkali metal salts (MX1/MX2, X1, X2 = Cl, Br, I, SCN,...
This report discloses a distinctive palladium‐catalyzed sequential tandem cyclization reaction of two molecular haloalkynes and one molecular N‐alkylanilines, leading to the efficient assembly of various 3‐halo‐1,2,5‐triarylpyrrole derivatives. Two carbon‐carbon triple bonds and one carbon‐halogen bond in two molecular haloalkynes are transformed conveniently in one single step, which may involve the aminoalkynylation of haloalkyne and cyclization of the newly formed enyne intermediate. The high chemo‐ and regioselectivities, good functional group tolerance and late‐stage modification of the halopyrrole products further illustrate the synthetic value of this strategy. This article is protected by copyright. All rights reserved.
A palladium-catalyzed Lewis acid-regulated cascade annulation of alkynes with unactivated alkenes for the preparation of alkyl substituted α-methylene-γ-lactones with excellent Z / E selectivities was accomplished.
Palladium‐catalyzed enantioselective cyclization of enynes has contributed significantly to the construction of chiral cyclic molecules. In contrast, the catalytic asymmetric cyclization involving halopalladation remains an unresolved challenge with the inevitable disturbance of the halide ions. Herein, an intramolecular chlorine transfer strategy is used to accomplish the enantioselective chloropalladation cyclization of 1,6‐enynes. This reaction provides a redox‐neutral approach to a variety of chiral α‐chloromethylene‐γ‐butyrolactones with excellent E selectivity and enantioselectivity. The precisely controlled coordination of palladium with both the in situ generated nucleophilic species and the monodentate phosphoramidite ligand is crucial for enantioselectivity.
A carboxylic acid-directed regioselective hydroarylation reaction of unactivated alkenes with aryl boronic acids was reported. This transformation was enabled by homogeneous manganese catalyst MnBr(CO)5 in the presence of KOH and H2O in the m-xylene reaction medium. Both internal and terminal alkenes worked well in this transformation, and a series of functional groups were tolerated. This reaction not only provided an expeditious method to prepare γ-aryl carboxylic acids from simple starting materials but also would inspire further studies in employing homogeneous manganese catalysis in organic synthesis.
A straight-forward approach to the synthesis of 3-bromoindoles via palladium-catalyzed oxidative C–H activation/annulation of N-alkylanilines with bromoalkynes has been described. This protocol features in high atom economy, excellent chemo- and...
Herein described a highly efficient palladium‐catalyzed cascade desulfitative arylation of acetylinic oximes and sodium arylsulfinates with oxygen as the sole oxidant to access structurally diverse 4‐aryl isoxazoles. This catalytic system exhibits mild conditions, broad substrate scope, and operational simplicity. Notably, other easily available aryl source substrates were perfectly tolerated in this catalytic system, thus providing a promising application in synthetic and pharmaceutical chemistry.
The first NHC-palladium-catalyzed regioselective oxyarylation of oxime ether in task-specific ionic liquid via C(sp3)-O and C(sp2)-O bond cleavage of two different type ethers for the assembly of structurally diverse 4-arylisoxazoles...
An efficient and straightforward palladium-catalyzed three-component cascade bisthiolation of terminal alkynes and arylhydrazines with sodium thiosulfate (Na2S2O3) as the sulfur source for the assembly of functionalized (Z)-1,2-bis(arylthio)alkene derivatives is described. Using 0.5 mol% IPr-Pd-Im-Cl2as the catalyst, a wide range of terminal alkynes and arylhydrazines are well tolerated, thus producing the desired products in good yields with good functional group tolerance and excellent regioselectivity. Moreover, this protocol could be readily scaled up, showing potential applications in organic synthesis and material science.
Main observation and conclusion
A novel and viable palladium-catalyzed sequential cyclization/functionalization of alkynone O-methyloximes and unactivated vinyl ethers under aerobic conditions was described. The structure of the products could be successfully controlled by varying the nature of the substituents of the vinyl ethers. This new approach provides the convenient and straightforward synthetic protocol for the preparation of structurally diverse 4-(1-alkoxyvinyl)-isoxazoles and 4-vinylisoxazoles in moderate to good yields with highly regioselectivity. Remarkably, this protocol can be performd on a gram scale, showing the promising application in synthetic and pharmaceutical chemistry.
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A TEMPO catalyzed cross-dihalogenation reaction was established via redox-regulation of the otherwise complex system of dual electrophilic X⁺ reagents. Formally, the ICl, BrCl, I2 and Br2 were generated in-situ, which enabled high regio- or stereoselective access to a myriad of iodochlorination, bromochlorination and homo-dihalogenation products with a wide spectrum of functionalities. With its mild conditions and operational simplicity, this method could enable wide applications in organic synthesis, which was exemplified by divergent synthesis of two pharmaceuticals. Detailed mechanistic investigations via radical clock reaction, pinacol ring expansion and Hammett experiments were conducted, which confirmed the intermediacy of halonium ion. In addition, a dynamic catalytic model basing on the versatile catalytic role of TEMPO was proposed to explain the selective outcomes.
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The hemilabile Ad2P(o-C6H4)NMe2 ligand promotes fast, quantitative and irreversible oxidative addition of alkynyl and vinyl iodides to gold. The reaction is general. It works with a broad range of substrates of various electronic bias and steric demand, and proceeds with complete retention of stereochemistry from Z and E vinyl iodides. Both alkynyl and vinyl iodides react faster than aryl iodides. The elementary step is amenable to catalysis. Oxidative addition of vinyl iodides to gold and π-activation of alkenols (and N-alkenyl amines) at gold have been combined to achieve hetero-vinylation reactions. A number of functionalized heterocycles, i.e. tetrahydrofuranes, tetrahydropyranes, oxepanes and pyrrolidines were obtained thereby (24 examples, 87% average yield). Taking advantage of the chemoselectivity for vinyl iodides over aryl iodides, sequential transformations involving first a hetero-vinylation step and then a C-N coupling, a C-C coupling or an heteroarylation were achieved from a vinyl/aryl bis-iodide substrate.
During the past decades, alkynes chemistry has attracted considerable attention owing to their unique and idiographic nucleophilic and electrophilic properties in transition-metal-catalyzed chemical transformations. Among the various metal catalysts, palladium...
Palladium‐catalyzed cascade cyclization received much attention in organic synthesis due to its efficiency and rapid transformation of simple starting materials into complex molecular skeletons. Celebrating the 10th year of the prestigious Nobel prize for palladium chemistry, we witness it still proceeds strong over other transition metals for its versatility. Cascade reactions in contemporary organic synthesis reduced cost and time through careful design. It has emerged as the first choice, a powerful tool for multiple bond formations in one step with a wide range of functional group tolerance due to the deep understanding of various pathways. A variety of compounds with biological relevance with complex molecular scaffolds have been achieved using these cascade coupling reactions. This review outlines Pd‐catalyzed cascade reactions from the post‐Nobel era. Nevertheless, more discoveries and endless possibilities for new transformations are underway.
A novel and practical palladium-catalyzed aerobic oxyarylthiolation of alkynone O-methyloximes for the assembly of 4-sulfenylisoxazole derivatives using S8 and arylhydrazines as the S-aryl sources is accomplished. In the presence of 0.1 mol% of IPr-Pd-allyl-Cl as the catalyst and O2 (1 atm) as the sole oxidant, both alkynone O-methyloximes and arylhydrazines are suitable substrates, delivering diverse 4-sulfenyl isoxazoles in moderate to good yields with good functional group tolerance. Notably, the phenyl diazonium salt and sodium phenyl sulfinate are also suitable arylation reagents, providing an alternative synthetic strategy to access structurally diverse 4-sulfenyl isoxazoles.
An efficient simple method was developed to prepare hetero E-1,2-dihaloolefins from mono- or disubstituted alkynes, in which, NXS (X=Br, I) was utilized as the electrophilic reagents and aqueous hydrohalic acid as the nucleophile. Moreover, Z-type dihalogenation olefins could be obtained from the terminal silylacetylene..
A palladium-catalyzed ionic liquids-accelerated oxidative cascade annulation/functionalization of acetylinic oximes with unactivated long-chain enols under aerobic conditions was accomplished. The newly developed protocol provides the rapid and straightforward synthetic strategy for the assembly of structurally diverse isoxazoles architectures under mild conditions with high atom- and step-economy and exceptional functional group tolerance. Notably, the ionic liquid acts as not only a solvent in the reaction, but also provides the excess halide ions to eliminate hydrochloride from acetylinic oximes. Moreover, this catalytic system could be recycled up to five times and reused without significant loss of catalytic activity.
Isoxazoles and their derivatives represent the privileged heteroaromatic motifs, which exhibit remarkable biological and pharmaceutical activities. Notably, metal catalyzed or mediated cyclization/functionalization of alkynes such as alkynone oxime ethers, acetylinic oximes, propargylic amino ethers, alkynyl nitrile oxides, and propargylic alcohols, have recently attracted much attention from synthetic organic chemists because of their high efficiency in the assembly of structurally diverse isoxazoles architectures under mild conditions with exceptional chemo-, stereo- and regioselectivities. In this review, a wide array of metal catalysts, such as palladium, copper, iron, gold, silver, and other metals have been summarized and discussed in details. Moreover, we also highlight some representative synthetic strategies and their transformation application along with reaction mechanisms involved during the reaction. And, the literature has been surveyed from 2010 until the beginning of 2020.
A novel and efficient palladium-catalyzed three-component cascade cyclization/arylthiolation for the assembly of diverse 3-sulfenylindoles and 3-sulfenylbenzofurans derivatives from 2-alkynylamines and 2-alkynylphenols, aryldiazonium salts, and Na2S2O3 under aerobic conditions with PEG-200 as an environmentally benign medium has been developed. The current study features exceptional functional group tolerance, without additional ligand or oxidant or silver salt, eco-friendly, and mild reaction conditions. Ionic liquids [C2OHmim]Cl as the environmental friendliness additive plays crucial roles in this protocol. Notably, this procedure represents the first example for the use of aryldiazonium salts as the direct S-arylation sources in this type chemical transformation.
Transition metal-catalyzed C-S bonds formation reactions have witnessed considerable attention in the recent years. In this regard, palladium-catalyzed C-S bonds formation is typically attractive, owing to its can effective assemble structurally diverse unsymmetrically aryl sulfides and functionalized sulfones under mild conditions with high regioselectivities. In this review, palladium-catalyzed C-S bonds formation reaction has been summarized and discussed in detail with the focus on sulfenylation and sulfonylation reaction involving aryl/heteroaryl C-H bonds, alkynes, aryl halides, electron-rich benzoic acid derivatives, arylhydrazines, and organosilicon reagents. We also highlight some representative synthetic strategies and their transformation application along with reaction mechanisms.
This updatetoScience of SynthesisSection 32.4 compiles methods for the synthesis of chlo-ro-, bromo-, and iodoalkanes reported since 2007. Starting materials include alkenylmetalcompounds, alkenes, haloalkanes, carbonyl compounds, enoic acids, alkynes, haloalkynes, and allenes, among others. The advantages and limitations of the different ap-proaches and methods are discussed, and mechanisms are described briefly in order to ra-tionalize regio- and stereoselectivities.
A palladium-catalyzed oxidative aminocarbonylation of O- methyloximes and simple amines under aerobic conditions with PEG-400 as environmentally benign media was accomplished. This novel protocol provides the first straightforward synthetic method for the assembly of structurally diverse 4-carboxamide isoxazoles with high atom- and step-economy and exceptional functional group tolerance. Notably, the employment of ionic liquids as additive, with air as the sole oxidant, without ligands are some of the attractive features of the present approach.
A novel tetrabutylammonium iodide (TBAI)-promoted three-component reaction of carboxylic acid with alkene and alcohol has been developed, which represents facile and straightforward access to polysubstituted γ-lactone skeletons in moderate-to-good yields. This methodology is distinguished by the use of a commercial catalyst and readily available starting materials, wide substrate scope, and operational simplicity. Mechanistic studies suggested that this transformation went through a radical process.
A nickel‐catalyzed conjunctive cross‐coupling of alkenyl carboxylic acids, aryl iodides, and aryl/alkenyl boronic esters is reported. The reaction delivers the desired 1,2‐diarylated and 1,2‐arylalkenylated products with excellent regiocontrol. To demonstrate the synthetic utility of the method, a representative product is prepared on gram scale and then diversified to eight 1,2,3‐trifunctionalized building blocks using two‐electron and one‐electron logic. Using this method, three routes toward bioactive molecules are improved in terms of yield and/or step count. This method represents the first example of catalytic 1,2‐diarylation of an alkene directed by a native carboxylate group.
Einfach wie 1, 2, 3: Unter Nickelkatalyse werden Alkenylcarbonsäuren selektiv 1,2‐diaryliert. Die dabei entstehenden Produkte können dann über klassische Carbonsäure‐Interkonversionen und moderne decarboxylierende Kreuzkupplungen problemlos in diverse 1,2,3‐trifunktionalisierte Motive umgewandelt werden.
Abstract
A nickel‐catalyzed conjunctive cross‐coupling of alkenyl carboxylic acids, aryl iodides, and aryl/alkenyl boronic esters is reported. The reaction delivers the desired 1,2‐diarylated and 1,2‐arylalkenylated products with excellent regiocontrol. To demonstrate the synthetic utility of the method, a representative product is prepared on gram scale and then diversified to eight 1,2,3‐trifunctionalized building blocks using two‐electron and one‐electron logic. Using this method, three routes toward bioactive molecules are improved in terms of yield and/or step count. This method represents the first example of catalytic 1,2‐diarylation of an alkene directed by a native carboxylate group.
A novel palladium-catalyzed, one-pot, four-step cascade method has been developed to afford functionalized γ-lactones in moderate to good yields. This novel and general methodology represents a rare instance of carbonylation of the C(sp(3))-palladium bond.
This review describes the recent advancement of transition metal-catalyzed aromatic carbon-boron bond construction processes. The efficacy of palladium, nickel and copper catalysis are comparatively illustrated. Particular focus is placed on the application of ligands, for instance tailor-made phosphines and carbenes that can effectively enable the borylation of challenging and sterically demanding substrates. Selected applications of this methodology for the synthesis of pharmaceutically useful and materially interesting molecules are mostly documented. This review includes literatures up to late 2012.
Potassium vinyltrifluoroborate was found to be an efficient partner with benzamide derivatives for Rh(III)-catalyzed annulations. 4-Trifluoroboratotetrahydroisoquinolones were generated under mild conditions, affording a regioisomerically complementary substitution pattern to other alkenes in related reactions. These new boron-containing building blocks were derivatized by N-arylations, retaining the boron substituent for further elaboration.
Paraconic acids, belonging to the class of γ-butyrolactone natural products, display a broad range of biological activities such as antibiotic and antitumor properties. Consequently a great number of synthetic strategies have been devised for them, ranging from diastereoselective and chiral pool approaches to the application of asymmetric catalysis. This review gives a critical account on the different methods developed that lead to paraconic acids of great structural variety.
Palladiumkatalysierte Kupplungen gehören zu den leistungsfähigsten und vielseitigsten Reaktionen, die dem organischen Chemiker für die Synthese zur Verfügung stehen. Ihre große Beliebtheit rührt teilweise daher, dass sie bei den Umsetzungen gewöhnlich viele funktionelle Gruppen tolerieren, was ihre breite Verwendung in vielen Bereichen ermöglicht. Allerdings unterlagen die palladiumkatalysierten Kupplungen jahrelang großen Einschränkungen durch die geringe Reaktivität der Arylchloride; diese Verbindungen sind in Bezug auf Kosten und Verfügbarkeit attraktivere Substrate als die entsprechenden Bromide, Iodide und Triflate. Herkömmliche Palladium/Triarylphosphan‐Katalysatoren setzten nur bestimmte aktivierte Arylchloride um (z. B. Heteroarylchloride und Substrate mit elektronenanziehenden Gruppen), nicht aber Arylchloride generell. Seit 1998 haben mehrere Forschungsgruppen bedeutende Fortschritte hinsichtlich dieser Herausforderung beschrieben; Katalysatoren mit voluminösen, elektronenreichen Phosphanen und Carbenen erwiesen sich als sehr vielseitig und ermöglichen besonders milde Reaktionsbedingungen. Dieser Aufsatz fasst die frühen, wegweisenden Arbeiten und die spannenden neuartigen Entwicklungen auf dem Gebiet der palladiumkatalysierten Kupplungen von Arylchloriden zusammen.
Collectively, palladium‐catalyzed coupling reactions represent some of the most powerful and versatile tools available to synthetic organic chemists. Their widespread popularity stems in part from the fact that they are generally tolerant to a large number of functional groups, which allows them to be employed in a wide range of applications. However, for many years a major limitation of palladium‐catalyzed coupling processes has been the poor reactivity of aryl chlorides, which from the standpoints of cost and availability are more attractive substrates than the corresponding bromides, iodides, and triflates. Traditional palladium/triarylphosphane catalysts are only effective for the coupling of certain activated aryl chlorides (for example, heteroaryl chlorides and substrates that bear electron‐withdrawing groups), but not for aryl chlorides in general. Since 1998, major advances have been described by a number of research groups addressing this challenge; catalysts based on bulky, electron‐rich phosphanes and carbenes have proved to be particularly mild and versatile. This review summarizes both the seminal early work and the exciting recent developments in the area of palladium‐catalyzed couplings of aryl chlorides.
A regioselective divalent palladium-catalyzed tandem coupling reaction of allenoic acids with alpha,beta-unsaturated carbonyl compounds was developed. The reaction involves intramolecular oxypalladation of an allene, followed by insertion of the alpha,beta-unsaturated carbonyl compound and protonolysis of the C-Pd bond to regenerate the Pd(II) species in the presence of excess halide ions. Functionalized lactones, tetrahydropyranones and dihydropyranones can be synthesized with high regioselectivity in one step.
Unsaturated bicyclic carboxylic acids undergo palladium-catalyzed coupling with bromoalkynes to produce γ-alkynyl lactones in moderate to good yields with excellent chemo- and regioselectivity. The reaction conditions were extremely mild, and functional groups such as methyl, methoxy, chloro, and bromo were tolerated under the optimized reaction conditions. Moreover, γ-chloroalkenyl lactones were facilely synthesized through chloropalladation/carboesterification of electron-deficient C≡C bonds by using molecular oxygen as the sole oxidant.
Alle(ne) großartig! Eine neue RhIII‐katalysierte oxidative Kupplung mit Allenen unter milden Bedingungen liefert Heterocyclen mit exocyclischen Doppelbindungen. Diese Reaktion benötigt nur geringe Katalysatormengen und bietet eine hohe Regio‐ und Stereoselektivität sowie eine exzellente Substratbreite. Es wurden eine Derivatisierung der Produkte sowie erste mechanistische Studien durchgeführt.
Mit Heck schnell ans Ziel: Die palladiumkatalysierte Aktivierung einer C(sp3)‐H‐Bindung durch einen in situ gebildeten σ‐Alkyl‐Palladium(II)‐Komplex ermöglicht einen neuartigen Dominoprozess aus Carbopalladierung und C(sp3)‐C(sp3)‐Verknüpfung, der rasch zu biologisch relevanten Spirooxindolen führt.
A Pd-catalyzed haloallylation of alkynes with allyl alcohols in ionic liquids has been reported. Both chloroallylation and bromoallylation can be easily carried out with high selectivity. A variety of 1,4-dienes were formed in moderate to excellent yields. The reaction system of the Pd catalyst as well as the ionic liquid can be recycled for several times. And the ionic liquid acts as not only a solvent in the reaction, but also provides the excess halide ions to control Z/E selectivity and acts as a ligand inhibit the β-hydride elimination.
A palladium-catalyzed regio- and stereoselective intermolecular tandem reaction of alkynes, and unactivated 1,6-enol in ionic liquids has been described, providing a practical, efficient, and versatile method for the synthesis of functionalized 1,6-dienes in moderate to good yields. The present reaction has high functional group tolerance and gives products in gram scale. Mechanistic studies indicate that the reaction might proceed via a chain-walking mechanism.
A Pd-catalyzed coupling of alkynes with homoallyl alcohols in ionic liquids has been reported, providing a practical, efficient, and versatile method for the synthesis of functionalized (1E)- or (1Z)-1,5-dienes in moderate to good yields. This reaction represents a rare instance of direct homoallylation of homoallyl alcohols.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
It has recently been found that alkylalane-zirconocene reagent systems can react with alkynes and alkenes via at least three different paths, i.e., (i) straightforward carbometallation without involving C-H activation, (ii) cyclic carbometallation via beta C-H activation, and (iii) hydrometallation. Various factors affecting the courses of such reactions have been delineated. In some cases, it is even possible to steer these reactions in the desired direction. Our recent development of a Zr-catalysed enantioselective alkene carboalumination reaction is an outgrowth of the above-mentioned systematic, exploratory, and mechanistic investigation.
Over the last 15 years, many approaches to the stereoselective C-C bond formation via the reaction of allylic metals with C=X electrophiles have been investigated. A variety of very successful methods have been developed for diastereoselective C-C bond formation between allylic metals and carbonyl compounds, imines, and alkenes. In many instances, high enantioselectivities have been achieved via the reactions of allylic boranes and stannanes. More recently, asymmetric allylation with catalytic amounts of certain Lewis acids has been reported. Main-group allylmetals always act as nucleophilic allyl transfer reagents, but transitionmetal allyl reagents exhibit both nucleophilic and electrophilic property depending on the metal (this review does not cover the latter reactions via π-allylpalladium complexes). New selectivities and reactivities have been observed in the reactions of transitionmetal allyl reagents including group 3 and Zr. Perfect regioselectivity has been accomplished with Ba reagents. Accordingly, in addition to the useful and common allyl reagents (B, Si, Sn, Ti, Cr), research on new types of allylmetals has just begun. Further investigations of the chemistry of allylmetals will provide us with a number of synthetically useful and selective reactions.
Spiro beta-lactone-based proteasome inhibitors were discovered in the context of an asymmetric catalytic total synthesis of the natural product (+)-lactacystin (1). Lactone 4 was found to be a potent inhibitor of the 26S proteasome, while its C-6 epimer (5) displayed weak activity. Crystallographic studies of the two analogues covalently bound to the 20S proteasome permitted characterization of the important stabilizing interactions between each inhibitor and the proteasome's key catalytic N-terminal threonine residue. This structural data support the hypothesis that the discrepancy in potency between 4 and 5 may be due to differences in the hydrolytic stabilities of the resulting acyl enzyme complexes.
A kinetic resolution process of Rh-catalyzed intramolecular Alder-ene reaction is described along with the studies of the substrate scope and stereochemistry of this remarkably efficient process. 3,4,5-Trisubstituted γ-lactones were synthesized in high enantioselectivity (>99% ee) and efficiency. The formal asymmetric syntheses of (−)-blastmycinolactol and (+)-blastmycinone, degradation products of the macrocyclic dilactone (+)-antimycin, were reported to address the applications of this methodology.
The Pd-catalyzed cyclizations of 1,6-enynes are efficient reactions for the synthesis of α-methylene-γ-butyrolactones and lactams. The effects of solvent, proton source, chloride concentration, and temperature on the protonolysis of the carbon–Pd bond were investigated and the optimal reaction conditions were identified. We showed that imidazolium-type ionic liquids played an important role in the reaction both as a ligand for the palladium catalyst and as a solvent. The crystal structure of the Pd complex was obtained and the reaction mechanisms were discussed.
Metallo-ene reactions, hardly recognized until very recently, have experienced a breathtaking development when applied in an intramolecular sense. Efficient regio- and stereoselective magnesium-ene cyclizations have served as a cornerstone for numerous syntheses of structurally diverse natural products (e.g., sesquiterpenes of marine or plant origin, alkaloids, fragrances, insect defense compounds, and a fungitoxin). A brilliant example is the synthesis of the elusive odorant (+)-khusimone which outshines 20 years of work in the field of tricyclovetivane synthesis. Palladium-, platinum-, and nickel-catalyzed versions of the metallo-ene reaction are in a comparatively early stage of exploration, but, nevertheless, reveal intriguing potential. Hence an almost 100% stereospecific CO→C;Pd-→ CC chirality transfer permits simple and selective, cis- or trans-annelation processes. The mild cyclization conditions are compatible with various functional groups, such as nitrogen moieties, which offer interesting perspectives for the preparation of heterocycles (e.g., alkaloids) difficult to obtain by other methods. Carbon monoxide insertion reactions of the cyclized σ-metal intermediates were shown to afford annelated cyclopentanones and cyclopentenones with concomitant stereocontrolled formation of four carbon–carbon bonds. These and other observations, highlighted in this article, provide a platform for further extensions and applications of this powerful method in organic synthesis.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A cheap and fast construction of both enantiomers of substituted succinimides is reported. α- or β-amino acids, such as β-phenylalanine and α-tert-butyl aspartate, were found to be efficient organocatalysts for the reaction between α,α-disubstituted aldehydes and maleimides. Products containing contiguous quaternary-tertiary stereogenic centers are obtained in high to quantitative yields and excellent selectivities utilizing low catalyst loadings (0.5-3.5%). Finally, a one-pot efficient asymmetric synthesis of lactones is described.
We describe herein a synthetically useful method for the enantioselective intermolecular Heck-Matsuda arylation of acyclic allylic alcohols. Aryldiazonium tetrafluoroborates were applied as arylating agents in the presence of Pd(TFA)2 and a chiral, commercially available, bisoxazoline ligand. The methodology is straightforward, robust, scalable up to a few grams, and of broad scope allowing the synthesis of a range of -aryl-carbonyl compounds in good to high enantioselectivities and yields. This new enantioselective Heck-Matsuda arylation allowed the synthesis of -aryl--lactones and -aryl aldehydes, which play a vital role as key intermediates in the synthesis of the biologically active compounds, such as (R)-baclofen, (R)-rolipram, (S)-curcumene, (S)-dehydrocurcumene, and (S)- tumerone.
A palladium-catalyzed approach for the synthesis of diarylmethanes from sodium sulfinates and benzyl chlorides is described. Various aromatic sodium sulfinates were used as aryl sources via extrusion of SO2 and gave the diarylmethanes in moderate to good yields.
Chiral NHCs catalyse the asymmetric formal [2+2]-cycloaddition of alkylarylketenes with both electron deficient benzaldehydes and 2- and 4-pyridinecarboxaldehydes to generate stereodefined beta-lactones. In the benzaldehyde series, optimal product diastereo- and enantiocontrol is observed using 2-nitrobenzaldehyde (up to 93:7 dr (syn:anti) and 93% ee). Substituted 2- and 4-pyridinecarboxaldehydes are also tolerated in this process, generating the corresponding beta-lactones in good yield and enantioselectivity, although the diastereocontrol in these processes is highly dependent upon the aldehyde substitution. These processes are readily scalable, allowing multi-gram quantities of the beta-lactone products to be prepared. Derivatisation of these products, either through ring-opening into the corresponding stereodefined beta-hydroxy- and beta-amino acid derivatives without loss of stereochemical integrity, or via cross-coupling, is demonstrated.
The HKR of racemic anti- or syn-3-substituted epoxy esters catalyzed by a Co(iii)salen complex provides ready access to the corresponding enantioenriched 3,4-disubstituted γ-butyrolactones and 3-substituted epoxy esters. This strategy has been successfully employed in the formal synthesis of biologically active 3,4-disubstituted piperidine derivatives, (-)-paroxetine and Ro 67-8867 and a natural product, (+)-eldanolide.
The article presents transition metal-mediated synthesis of monocyclic aromatic heterocycles. The development of selective and general methods for a facile assembly of the diversely substituted furan core attracted tremendous interest over the past few decades. Consequently, numerous reviews covering a large number of existing synthetic methods toward furans via a modification of preexisting heterocyclic core and assembly of the ring from acyclic precursors have appeared. Gevorgyan and co-workers demonstrated that easily available conjugated alkynyl ketones could indeed serve as highly versatile surrogates of somewhat unstable and not so simply accessible allenones, which are typically used in many efficient furan syntheses. Bearing in mind the development of milder and safer conditions for cycloaddition of nitriles and azides, Bosch and Vilarrasa developed the Cu(I)-catalyzed synthesis of 1,5-disubstituted tetrazoles.
Heck shortens the distance: A method for the palladium-catalyzed activation of a C(sp(3) )H bond by a σ-alkyl Pd(II) complex generated in situ from a remote arylhalide function has been developed. This allows a novel domino carbopalladation/ C(sp(3) )C(sp(3) ) bond-forming process to provide rapid access to biologically relevant spirooxindoles.
The integral role of halide ions as a ligand in the reactions of stoichiometric arylpalladium reagents and Pd(II)-catalyzed reaction of phenylmercuric acetate with various allylic compounds were studied. The halide ion was found to inhibit β-H elimination and promote β-heteroatom elimination in acidic media. In this reaction, a C−Pd intermediate with a β-heteroatom (including halogen, acetoxy, alkoxy, and hydroxyl groups) gives only β-heteroatom elimination product in the presence of halide ions, while β-H elimination is effectively blocked.
The reaction of various acetylenes and allyl halides with palladium complexes selectively gives substituted 1,4-, diene codimers. The PdX2(PhCN)2 complex is the most active catalyst. In contrast to substituted acetylenes, the reaction of acetylene itself and allyl halides gives a 1-halogeno-1,3,6-heptatriene cotrimer besides codimers. The catalytic reaction proceeds via Pd-halogen bond recycle; initially acetylene inserts into a Pd-halogen bond and subsequently allyl halide inserts into a Pd-vinyl bond, followed by the β-halogen elimination to give a codimer. The successive insertions of acetylene and allyl halide into the Pd-vinyl bond give a cotrimer. This codimerization provides a very convenient synthetic method for halogeno-substituted mono- and/or diolefins.
Herein, we describe a new convergent synthesis of a more potent analogue of clasto-lactacystin β-lactone (2), PS-519 compound 4, which is currently in preclinical development for the treatment of ischemia−reperfusion injury in stroke and myocardial infarction. The synthetic strategy relies on building two intermediates (an oxazoline and an aldehyde) which are joined through a doubly diastereoselective aldol reaction, setting up the requisite unichiral centers in the final product (4). The facial selectivity and ultimate stereocontrol are achieved by employing a trivalent aluminum Lewis acid, Me2AlCl, in a chelation-induced reaction which yields a single aldol adduct. The efficiency of the synthetic approach has allowed for the preparation of multigram quantities of clinical grade material, which will support Phase I studies.
Antimycic acid, a degradation product of antimycin A, has been shown to be N-(3-aminosalicyloyl)-L-threonine by hydrolysis to L-threonine and 3-aminosalicylic acid.
The synthesis of lactones in high yields by the palladium-catalyzed carbonylation reaction of halo alcohols can be effected under mild conditions (1-4 aim CO, 25-60°C) with a high turnover of palladium. Benzyl, allyl, aryl, and vinyl halides containing primary, secondary, or tertiary alcohol groups are readily converted to a variety of lactones, including phthalides and butenolides, by this simple procedure.
A novel Au-catalyzed tandem cycloisomerization/oxidation of homopropargyl alcohols was developed. Various γ-lactones can be accessed readily by utilizing this strategy. Notably, the mechanism of this reaction is distinctively different from the related Ru-catalyzed reactions where the ruthenium vinylidene intermediate was proposed.
Oxidation reactions are central components of organic chemistry, and modern organic synthesis increasingly requires selective and mild oxidation methods. Although researchers have developed new organic oxidation methods in recent years, the chemistry community faces continuing challenges to use “green” reagents and maximize atom economy. Undoubtedly, with its low cost and lack of environmentally hazardous byproducts, molecular oxygen (O2) is an ideal oxidant. However, relatively limited methodologies are available that use O2 efficiently in selective organic transformations.
Metallo-En-Reaktionen waren bis vor wenigen Jahren kaum bekannt. Ihre intramolekularen Varianten entwickelten sich nun in jüngster Zeit auf beeindruckende Weise. Der strategische Einsatz stereoselektiver Magnesium-En-Cyclisierungen ermöglicht ergiebige Synthesen zahlreicher, strukturell sehr verschiedener Naturstoffe (z. B. Sesquiterpene marinen und pflanzlichen Ursprungs, Alkaloide, Riechstoffe, insekteneigene Abwehrstoffe, Fungitoxine). Ein brillantes Beispiel ist die Synthese des olfaktisch interessanten, aber schwer zugänglichen Tricyclovetivens (+)-Khusimon, die 20 Jahre Arbeit zum Aufbau dieser Substanzklasse in den Schatten stellt. Palladium-, Platin- und Nickel-katalysierte Versionen befinden sich noch im Anfangsstadium der Erforschung, zeigen aber bereits ein faszinierendes Spektrum von Möglichkeiten. Ein nahezu 100% stereospezifischer C-O-→C-Pd-→C-C-Chiralitäts-Transfer erschließt einfache und selektive cis- und trans-Anellierungen. Die milden Reaktionsbedingungen sind mit vielen funktionellen, u. a. stickstoffhaltigen Gruppen kompatibel; damit eröffnen sich interessante Perspektiven zur Herstellung von Heterocyclen (z. B. Alkaloiden). Abfangreaktionen der cyclisierten σ-Metall-Zwischenprodukte unter Einschiebung von Kohlenstoffmonoxid führen zu anellierten Cyclopentanonen und Cyclopentenonen, wobei „gleichzeitig” und stereokontrolliert vier CC-Bindungen gebildet werden. Die hier und im folgenden vorgestellten Beobachtungen bieten eine Grundlage zur weiteren Erforschung und Anwendung dieser leistungsfähigen Methode in der Organischen Synthese.
Seit einigen Jahren erlebt die Forschung an α-Methylen-γ-butyrolactonen einen enormen Aufschwung. Diese Übersicht beschreibt die Strukturen, die biologische Aktivität und die Biosynthese der Substanzen mit dem Schwerpunkt auf Veröffentlichungen aus den letzten zehn Jahren. Thematisiert werden sowohl die klassischen Herstellungsmethoden von α-Methylen-γ-butyrolactonen und α-Alkyliden-γ-butyrolactonen als auch neue Syntheseansätze, die unter anderem von uns entwickelt worden sind.
The amount of research activity concerning alpha-methylene-gamma-butyrolactones and alpha-alkylidene-gamma-butyrolactones has increased dramatically in recent years. This Review summarizes the structural types, biological activities, and biosynthesis of these compounds, concentrating on publications from the past 10 years. Traditional approaches to alpha-methylene-gamma-butyrolactones and alpha-alkylidene-gamma-butyrolactones are then reviewed together with novel approaches, including those from our own research group, reported more recently.
Palladiumkatalysierte Kupplungen gehören zu den leistungsfähigsten und vielseitigsten Reaktionen, die dem organischen Chemiker für die Synthese zur Verfügung stehen. Ihre große Beliebtheit rührt teilweise daher, dass sie bei den Umsetzungen gewöhnlich viele funktionelle Gruppen tolerieren, was ihre breite Verwendung in vielen Bereichen ermöglicht. Allerdings unterlagen die palladiumkatalysierten Kupplungen jahrelang großen Einschränkungen durch die geringe Reaktivität der Arylchloride; diese Verbindungen sind in Bezug auf Kosten und Verfügbarkeit attraktivere Substrate als die entsprechenden Bromide, Iodide und Triflate. Herkömmliche Palladium/Triarylphosphan-Katalysatoren setzten nur bestimmte aktivierte Arylchloride um (z. B. Heteroarylchloride und Substrate mit elektronenanziehenden Gruppen), nicht aber Arylchloride generell. Seit 1998 haben mehrere Forschungsgruppen bedeutende Fortschritte hinsichtlich dieser Herausforderung beschrieben; Katalysatoren mit voluminösen, elektronenreichen Phosphanen und Carbenen erwiesen sich als sehr vielseitig und ermöglichen besonders milde Reaktionsbedingungen. Dieser Aufsatz fasst die frühen, wegweisenden Arbeiten und die spannenden neuartigen Entwicklungen auf dem Gebiet der palladiumkatalysierten Kupplungen von Arylchloriden zusammen.
In this tutorial review, we will summarize our recent efforts in transition metal-catalyzed oxidative coupling via C-H functionalization of aromatic, benzylic and allylic C-H bonds. Related works from other laboratories will be cited where suitable, aiming to give the readers a flavor of this field. Special emphasis is placed on the reaction design and development.
Various β-lactones were prepared from β-hydroxycarboxylic acids by intramolecular dehydration condensation using MNBA, an effective coupling reagent, along with a nucleophilic catalyst. The transition state that provides the desired 4-membered ring model system is disclosed by density functional theory (DFT) calculations, and the structural features of the transition form are discussed. This method was successfully applied to the asymmetric total synthesis of tetrahydrolipstatin (THL), an antiobestic drug used in clinical treatment to inhibit the activity of pancreatic lipase.
Three in one: A highly efficient and mild Pd(II) -catalyzed carboesterification of alkenes with carboxylic alkyne derivatives proceeds through a domino-type alkyne-alkene coupling/CO-bond formation. The stereoselectivity is controlled by the choice of substrates and temperature. The reaction provides a convenient method for the construction of naturally occurring biologically active compounds with α-methylene-γ-lactone skeletons.
All(enes) great! A novel Rh(III)-catalyzed oxidative coupling with allenes under mild conditions provides heterocycles with exocyclic double bonds. This reaction features low catalyst loadings, high regio- and stereoselectivity, and excellent substrate scope. The products were derivatized and preliminary mechanistic studies were conducted.
Ruthenium-catalyzed oxidative C-H bond olefination of N-methoxybenzamides using an oxidizing directing group with a broad substrate scope is reported. The reactions of N-methoxybenzamides with acrylates in MeOH and styrene (or norbornadiene) in CF(3)CH(2)OH afforded two types of products.
An efficient protocol has been developed for the intramolecular oxidative oxyarylation using a Pd(II) -catalyzed tandem oxypalladation/CH functionalization strategy. This methodology allows rapid access to tetrahydro-2H-indeno-[2,1-b]furan frameworks from simple hydroxyalkenes. The reactivity of this process is orthogonal to that of Pd(0) -catalyzed transformations, enabling the divergent modification of a single molecule.
A palladium-catalyzed intramolecular oxidative aryltrifluoromethylation reaction of activated alkenes has been explored. The reaction allows for an efficient synthesis of a variety of CF(3)-containing oxindoles. Preliminary mechanistic study indicated that the reaction involves a C(sp(3))-Pd(IV)(CF(3)) intermediate, which undergoes reductive elimination to afford a C(sp(3))-CF(3) bond.