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ChemInform Abstract: Palladium-Catalyzed Migratory Insertion of Isocyanides: An Emerging Platform in Cross-Coupling Chemistry.
Angewandte Chemie International Edition
Abstract
Isocyanides have been important building blocks in organic synthesis since the discovery of the Ugi reaction and related isocyanide-based multicomponent reactions. In the past decade isocyanides have found a new application as versatile C1 building blocks in palladium catalysis. Palladium-catalyzed reactions involving isocyanide insertion offer a vast potential for the synthesis of nitrogen-containing fine chemicals. This Minireview discusses all the achievements in this emerging field.
... This makes it an attractive metal for the development of more sustainable catalytic synthetic methodologies towards high added value chemicals. [2] Also in the field of imidoylative cross-coupling reactions, [3,4] which employ isocyanides as versatile C1 building blocks, [5] moving away from traditional noble metals towards of base metals (such as iron) seems highly attractive. A relatively underexplored reaction in this area is the TM-catalysed carbene transfer to isocyanides (Scheme 1A). ...
... [10] Although iron complexes have been used as catalysts in carbene transfer reactions to various functionalities, [11,12] their use in carbene transfer to isocyanides is unprecedented. [13] Here we report the use of the nucleophilic ferrate complex Bu 4 N[Fe-(CO) 3 NO] (TBA[Fe]), [12,14] also referred to as the Hieber anion, as a suitable catalyst for carbene transfer to isocyanides (1). In this process diazo compounds (2) are employed as readily available carbene precursors (Scheme 1B). ...
... [ 1 [b] FeCl 3 --DCE 22 2 [b] Fe(TPP)Cl --DCE 35 3 [b] Fe(TPP)Cl -Zn (50) DCE 40 4 [b] Fe(Pc) --DCE 75 5 [b] FeCl 2 --DCE trace 6 [b] FeCl 2 L1 (6) NaBAR F (6) DCE trace 7 [b] Fe(ClO 4 ) 2 .4H 2 O --DCE 40 8 [b] Fe(ClO 4 ) 2 .4H 2 O L1 (6) NaBAR F (6) DCE 68 9 [b] Fe(ClO 4 ) 2 .4H 2 O L2 (6) NaBAR F (6) DCE 7 10 [b] Fe(CO) 5 --DCE 77 11 [b] TBA challenging in transition metal-catalysed reactions with these isocyanides. [3,4] Incorporation of an ether functionality in isocyanide 1 f gave pyrimidinone 4 fa in 40 % yield. Next, we investigated isocyanides featuring an activated methylene group. ...
An iron‐catalysed carbene transfer reaction of diazo compounds to isocyanides has been developed. The resulting ketenimines are trapped in situ with various bisnucleophiles to access a range of densely functionalized heterocycles (pyrimidinones, dihydropyrazolones, 1H‐tetrazoles) in a one‐pot process. The electron‐rich Hieber anion ([Fe(CO)3NO]⁻) facilitates efficient catalytic carbene transfer from acceptor‐type α‐diazo carbonyl compounds to isocyanides, providing a cost‐efficient and benign alternative to similar noble metal‐catalysed processes. Based on DFT calculations a plausible reaction mechanism for activation of the α‐diazo carbonyl carbene precursor and ketenimine formation is provided.
... Owing to their unique reactive properties of isonitrile functionality, isocyanides have become ponderable building blocks in synthetic chemistry. In general, isocyanides are regarded as isoelectronic with carbon monoxide, and could undergo typical insertion reactions [19][20][21]. The common insertion mode is that a radical attacks an isocyanide moiety to afford imidoyl radicals, which could be further coupled with the second radical or radical acceptors such as arenes [22][23][24]. ...
... Then, O-acylated acyl oximes including C6H5CO, C6F5CO, p-FC6H4CO, p-NO2C6H4CO, p-OMeC6H4CO, and CH3CO were investigated, which indicated that the O-p-CF3C6H4CO acyl oxime was the most effective acyl precursor (entries [11][12][13][14][15][16]. The screening of other solvents, such as CH3CN, THF, DCE, n BuOAc, toluene, and DMSO, showed that DMF was the optimal solvent for the photoinduced acyl transfer reaction (entries [17][18][19][20][21][22]. In addition, the acylation/cyclization reactions could occur at 80 °C or 120 °C, albeit with a low yield of 3aa (entries [23][24]. ...
An efficient acylation/cyclization reaction of 6-acyl phenanthridines with oxime esters using photoredox catalysis has been developed. This radical acyl transfer strategy enables a facile access to acyl-substituted phenanthridines with good yield and excellent selectivity. The developed method is redox neutral and has broad substrate scope and excellent functional group tolerance.
... Inspired by these successes, the functional group −NC has caught our attention, because it has a special feature with two main resonance forms: exhibiting an isoelectronic (akin to CO) triple bond or being carbenoid with a double bond. 36,37 The chameleonic nature of −NC allows its carbon atom to act as a nucleophile, 38−40 an electrophile, 41 a carbene, 42 or a radical. 43−45 The presence of a lone pair on the terminal carbon atom endows the −NC group with strong coordinative properties, not only for metal complexation. ...
... b A, B, and C are the rotational constants. The experimental values of the centrifugal distortion constants D J , D JK , D K , as well as d 1 are determined to be 0.360(13), −1.305 (26), 0.977 (37), and 0.0439(55) kHz, respectively. χ aa , χ bb , and χ cc are the diagonal elements of the 14 N nuclear quadrupole coupling tensor, which are the same for the two 14 N nuclei due to the symmetry. ...
Phenyl isocyanide has been chosen as a prototype to probe the π-π interaction modulated by the -NC group, which has a chameleonic nature with two main resonance forms showing a triple bond and being carbenoid. The rotational spectroscopic investigation complemented with theoretical analyses indicates that the phenyl isocyanide dimer has a scissor-like configuration controlled by dispersive forces along with the formation of π-π stacking. This is the first rotational spectroscopic evidence, to the best of our knowledge, that the mono-substitution by an -NC group on benzene can activate the meta position in forming noncovalent interactions. This work also provides experimental evidence on the importance of substituent effects in modulating π-π stacked structures, as well as practical proof of a biased interaction behavior of isocyanide-substituted aromatic molecules.
... [131][132][133] They have also been used in the pharmaceutical and fine chemical sectors. [76,[134][135][136][137][138] ...
A transition metal-free, base mediated approach has been devised for the synthesis of novel densely functionalized alkenes containing isocyanide, nitrile and ester functionalities. The strategy was found applicable to gram-scale synthesis and a library of functionalized alkenes with significant diversity was developed. It was found that strategy could also be used for the synthesis of trisubstituted pyrrole derivatives by modifying the reaction conditions. The advantages of this approach are operationally simple procedure, short reaction time (10-30 min), broad substrate scope, high atom economy, metal-free conditions, and high regioselectivity with good to excellent product yields.
A palladium-catalyzed cascade cyclization reaction of di-o-iodophenyl sulfonylguanidines with isocyanides for the efficient and selective synthesis of 5- or 6-membered heterocyclic fused quinazolines has been developed. Diverse functional groups are...
Past decades have witnessed significant advance of isocyanides as a class of versatile organic synthons as well as their broad applications in multi-component reactions (MCRs) and other tandem reactions. Reactions involving multiple isocyanides allow the construction of molecules with further diversification and complexity, while C-H functionalization emphasizes the advantages of high atom economy, broad substrate availability and great synthetic efficiency. This promising synergistic strategy of C-H functionalization involving multiple isocyanides provides a variety of valuable synthetic methods for organic chemists' toolbox and offers considerable potential in pharmaceutical chemistry and materials science as well. The present review outlines in detail various reaction types of C-H functionalization enabled by multiple isocyanides, and the relevant mechanistic rationale is discussed.
In this investigation, N-substituted phosphinecarboxamides were produced through the reaction of [TBA][P(SiCl3)2] with isonitriles. This method capitalizes on the flexibility of isonitriles as a source of both nitrogen and carbonyl groups, offering a novel route to the generation of PH2-type compounds. This approach is characterized by rapid reaction times, simple procedural requirements, compatibility with a diverse array of substrates, and the conversion of [TBA][P(SiCl3)2] into organic phosphorus compounds. Additionally, we systematically studied the reaction mechanism of isonitrile with [TBA][P(SiCl3)2] through controlled experiments and density functional theory (DFT) calculations.
Isocyanides are an important class of building blocks in synthetic organic chemistry, however, the difunctionalzation of isocyanide still presents significant challenges. Herein, we developed metal free mediated difunctionalzation of isocyanides...
Precisely controlling the product selectivity of a reaction is an important objective in organic synthesis. α‐Ketoamides are vital intermediates in chemical transformations and privileged motifs in numerous drugs, natural products, and biologically active molecules. The selective synthesis of α‐ketoamides from feedstock chemicals in a safe and operationally simple manner under mild conditions is a long‐standing catalysis challenge. Herein, an unprecedented TBD‐switched Pd‐catalyzed double isocyanide insertion reaction for assembling ketoamides in aqueous DMSO from (hetero)aryl halides and pseudohalides under mild conditions is reported. The effectiveness and utility of this protocol are demonstrated by its diverse substrate scope (93 examples), the ability to late‐stage modify pharmaceuticals, scalability to large‐scale synthesis, and the synthesis of pharmaceutically active molecules. Mechanistic studies indicate that TBD is a key ligand that modulates the Pd‐catalyzed double isocyanide insertion process, thereby selectively providing the desired α‐ketoamides in a unique manner. In addition, the imidoylpalladium(II) complex and α‐ketoimine amide are successfully isolated and determined by X‐ray analysis, confirming that they are probable intermediates in the catalytic pathway.
Mono or bis(tetrazole-thiolato) Pd(II) or Pt(II) complexes were obtained from dialkyl Pd(II) or Pt(II) complexes with organic tetrazole-thiones (1-aryl or 1-alkyl-1H-tetrazole-5-thiones) via deprotonation. In contrast, equimolar reactions of zerovalent Pt(0)...
An efficient heterogeneous palladium-catalyzed carbonylative coupling of aryl halides and organoaluminum compounds has been developed using tert-butyl isocyanide as CO equivalent. The carbonylation reaction proceeds smoothly in toluene with KOtBu as a base at 100 °C by using 10 mol% of an SBA-15-anchored bidentate phosphine palladium(0) complex [2P-SBA-15-Pd(0)] as the catalyst and provides a general and practical approach for the assembly of 1,2-diketones in good to excellent yields. This heterogenized palladium catalyst can be readily separated and recovered via a simple centrifugation process and reused for more than seven cycles with almost consistent catalytic efficiency.
Precise control on the product selectivity of a reaction is an important objective in organic synthesis. α-ketoamides are vital intermediates in chemical transformation and privileged motifs in numerous drugs, natural products and biologically active molecules. The selective synthesis of α-ketoamides from feedstock chemicals in a safe and operationally simple manner under mild conditions is a long-standing challenge in catalysis. Herein we disclose an unprecedented TBD-switched Pd-catalyzed double isocyanide insertion reaction of (hetero)aryl halides or pseudohalides for the assembly α-ketoamides in aqueous DMSO under mild conditions. The effectiveness and utility of this protocol are demonstrated by diverse substrate scope (85 examples), late-stage modification of pharmaceuticals, scalability in large-scale synthesis, transformations of functional groups, as well as the synthesis of pharmaceutically active molecules. Mechanistic studies indicate that TBD is a key ligand to modulate the Pd-catalyzed double isocyanide insertion process, thus selectively providing the desired α-ketoamides in a unique manner. In addition, imidoylpalladium(II) complex and α-ketoimine amide are successfully isolated and determined by X-ray analysis, proving them the probable intermediates in the catalytic pathway.
A visible-light-induced radical cyclization reaction of o-vinylaryl isocyanides and oxime esters to access various 2,4-disubstituted quinolines was disclosed. Oxime esters were employed as acyl radical precursors via the carbon−carbon bond...
Cyanation has attracted considerable attention in organic synthesis because nitriles are key structural motifs in numerous important dyes, agrochemicals, natural products and drug molecules. As the fourth generation of cyanating reagents, isocyanides occupy a prominent place in the synthesis of nitriles due to their favorable stability, easy operability and high reactivity. In recent years, three types of cyanation with isocyanides have been established: the cleavage of the C-NC bond of tertiary alkyl isocyanides (Type I), the rearrangement of aryl isocyanides with azides (Type II), and the reductive cyanation of ketones with α-acidic isocyanides (Type III). This review focuses on advances in cyanation with isocyanides with an emphasis on reaction scope, limitations and mechanisms, which could reveal their remarkable value and superiority for accessing various nitriles. In addition, the future development prospects of this specific field are also introduced. We believe that this feature article will serve as a comprehensive tool to navigate cyanation with isocyanides across the vast area of synthetic chemistry.
A photoredox radical cascade cyclization reaction for the effective construction of 2,4-disubstituted quinolines at room temperature is described. It shows good substrate suitability and functional group compatibility.
Tryptamine-derived isocyanides are valuable building blocks in the construction of spirocyclic indolenines and indolines via dearomatization of the indole moiety. We report the Bu4N[Fe(CO)3NO]-catalyzed carbene transfer of α-diazo esters to 3-(2-isocyanoethyl)indoles, leading to ketenimine intermediates that undergo spontaneous dearomative spirocyclization. The utility of this iron-catalyzed carbene transfer/spirocyclization cascade was demonstrated by its use as a key step in the formal total synthesis of monoterpenoid indole alkaloids (±)-aspidofractinine, (±)-limaspermidine, (±)-aspidospermidine, and (±)-17-demethoxy-N-acetylcylindrocarine.
Cleavage of C(CO)-C bonds is a fascinating transformation that offers exciting opportunities for development of new synthetic methodologies through reconstruction of the molecular skeleton. However, the catalytic insertion of heteroallenes...
The domino process of the palladium-catalyzed coupling reaction of isocyanides with 2H-azirine provides various tetrasubstituted pyrimidines via one C-C bond and two C-N bond formations with satisfactory yields. The title compounds are obtained with good functional group tolerance, high atom economy, and broad substrate scopes.
Catalytic functionalization of indoles has been one of the most flourishing topics in organic chemistry. However, most known methods for the synthetic modifications of indoles take place at the C3...
A cobalt(II) mediated three-component synthesis of 5-substituted-N-sulfonyl-1,3,4-oxadiazol-2(3H)-imines using sulfonyl azides, N-isocyaniminotriphenylphosphorane (NIITP), and carboxylic acids has been developed. This one-pot tandem reaction starts with a nitrene transfer to NIITP, followed by addition of the carboxylic acid to the in situ formed carbodiimide and subsequent intramolecular aza-Wittig reaction. Both the steric constraints of carboxylic acid and the stoichiometry of the employed cobalt salt determine the selectivity toward the two products, i.e. 5-substituted-N-sulfonyl-1,3,4-oxadiazol-2(3H)-imine versus 5-substituted-4-tosyl-2,4-dihydro-3H-1,2,4-triazol-3-one.
In recent years, the silver‐catalyzed and silver‐promoted isocyanide reactions have attracted much attention, due to its efficiency in the formation of diverse new bonds and good reaction selectivity. A series of highly useful linear or cyclic compounds have been constructed. In this review, the recent progress in this field is described in the sequence of synthesis of five‐membered heterocyclic compounds, synthesis of six‐membered heterocyclic compounds, synthesis of fused cyclic compounds as well as synthesis of linear nitrogen‐containing compounds.
A consecutive four-component alkynylation-amine addition-nitroalkene addition-cyclocondensation one-pot reaction of acid chlorides, alkynes, amines and nitroalkenes furnishes a library of 3-acyl pyrroles in modest to good yields. The sequence takes advantage of a synergism between Brønsted acid (acetic acid) and Lewis acid (iron(III) chloride) in the terminal addition-cyclocondensation step of the intermediary formed enaminones with nitroalkenes.
Herein, we describe a nickel-catalyzed divergent formylation and carboxylation reaction of aryl halides with isocyanides. A rich array of aromatic aldehydes and carboxylic acids can be, respectively, accessed in moderate to good yields. Some sensitive functional groups such as hydroxyl, iodine, cyano, and indolyl are fairly tolerant of nickel catalysis. In the carboxylation reactions, the combination of isocyanide and H2O is first employed as a promising carbonyl surrogate instead of gaseous CO and CO2.
A highly efficient SnCl4-catalyzed nucleophilic isocyanation of cyclopropyl ethers has been developed. The reaction proceeds at the quaternary carbon stereocenter of the cyclopropane with a complete inversion of configuration, providing a new avenue for the construction of synthetically challenging tertiary alkyl isonitriles with high diastereopurity. The diversity of the incorporated isocyanide group has been demonstrated by the transformation of tertiary alkyl isonitriles into the corresponding tertiary alkyl amines, amides, and cyclic ketoimines.
Isocyanides have been extensively utilized in organic synthesis to construct valuable chemical structures. Classical Ugi 4‐component reaction is the robust method to access diversely functionalized peptoids. By using well‐established cyclization techniques, a variety of nitrogen heterocycles from commercially accessible compounds have been efficiently synthesized. Several transition metal‐catalyzed processes have been developed to utilize isocyanide as a useful carbonyl nitrogen synthon. Recently developed synthetic methods, such as C–H bond activation and visible‐light photocatalysis, have been adopted to the isocyanide chemistry to enhance the efficiency, availability, and novelty of the chemical processes. This review summarizes the reactivity of isocyanide classified by the activation modes of electrophilic, nucleophilic, and radical species, together with the seminal discoveries and recent advances in the past 10 years.
A remarkably efficient protocol for the mediation of Mn(III) to the radical addition/cyclization cascade of boronic acids with isocyanides leading to 3‐aminoquinoline derivatives is established. A reasonable explanation to the high reactivity of the Mn(III) salt was suggested. Application of the synthetic method to the late‐stage modification of drug molecules was also presented.
An efficient Mn(III)-promoted cascade reaction of tryptamine-derived isocyanides with arylboronic acids for access to spiroindoline derivatives is described. The reaction undergoes a radical addition/spirocyclization pathway, providing spiroindolines in good yields...
An efficient TMSOTf-promoted selective triple consecutive insertions of tert-butyl isocyanide into aldehydes has been developed, affording pharmacological interesting 4-cyanooxazoles in high yields in a one pot manner. The given method encompasses a wide range of substrates with tert-butyl isocyanide serving as sources of critical "CN" and "C-N═C" moieties. The versatile transformations of the resulting 4-cyanooxazoles were demonstrated. The key reaction intermediates for plausible mechanisms were determined.
The three-component domino reaction of thioamides, benzyl isocyanide, and water in the presence of a catalytic amount of both Pd(dppf)Cl2 and Cu(OAc)2 afforded novel 1,2,4-thiadiazolidin-3-one cyclic compounds, whereas the same reaction with tertiary alkylisonitriles in the presence of rare earth metal salt [La(OTf)3] resulted in (E)-N-(1,2-diamino-2-thioxoethylidene)benzamide open-chain products. This divergent reaction enabled the one-pot construction of five (N-S, C-S, C-O, and two C-N) or four (C-S, C-N, C-O, and C-C) new chemical bonds. Mechanism studies indicate that the oxygen atom of the product was derived from H2O.
A novel strategy to access unsymmetrically linked heterocycles via palladium-catalyzed acylcycloimidoylation of alkyne-tethered carbamoyl chlorides with isocyanides has been developed. Functionalized isocyanides were successfully applied as imine-containing heterocycle precursors to capture the vinyl-PdII intermediate, which was generated from a syn-carbopalladation of alkyne, followed by subsequent intramolecular C-H bond activation/imidoylative Heck reactions. Methylene oxindoles within Z-tetrasubstituted olefins were obtained in high yields with excellent stereoselectivities. Broad functional groups were well tolerated under mild reaction conditions.
The structure of isocyanide-phosphine complexes of palladium(II) dihalides [PdX2(CNR)(PPh3)] (X = Cl, Br, I; R = t-Bu, Xyl, and Mes) in CDCl3 solutions and in solid phase, and also their resistance to cis/trans isomerization and ligands disproportionation were studied. The isocyanide-phosphine complexes of palladium(II) chloride, bromide, and iodide in crystals take the cis configuration. In solution isocyanide-phosphine complexes of palladium(II) chloride and bromide exist predominantly in the cis configuration. They are resistant to ligand disproportionation and can be prepared by mixing equivalent amounts of the corresponding bisisocyanide and bisphosphine complexes. In contrast, mixed-ligand isocyanide-phosphine complexes of palladium iodide in solution rapidly form mixtures of cis and trans isomers, and also of bisisocyanide and bisphosphine complexes.
Stereoselective difunctionalizations of the terminal and internal alkynes with various sulfinates and isocyanides have been achieved to prepare (Z)-/(E)-β-sulfonylacrylamides. The (Z)-β-sulfonylacrylamides were generated via a one-pot process that involves the reaction of terminal alkynes with sulfinates and isocyanides in the presence of iodine in sequential manner. The (E)-β-sulfonylacrylamides were prepared in a two-step synthesis via palladium(II)-catalyzed addition of isocyanide to (E)-β-iodovinylsulfones synthesized from alkynes.
Non-noble cobalt catalysts have been employed in various C-H bond activation and functionalization in recent years. Herein, we report a cobalt-catalyzed C-H activation and isocyanide insertion of 1H-indole-3-carboxamides for the divergent synthesis of two types of indole-containing molecules. Notably, the reaction with MgSO4 as the additive produces 1H-indole-2,3-dicarboxamides, while PivOK promotes the formation of 3-imino-3,4-dihydropyrrolo[3,4-b]indol-1(2H)-ones in moderate to high yields. Control experiments reveal that 3-imino-3,4-dihydropyrrolo[3,4-b]indol-1(2H)-ones is likely to be transformed to 1H-indole-2,3-dicarboxamides via the nucleophilic attack of H2O in the reaction system.
Herein, We report a cascade reaction of intramolecular indolyl isocyanide-insertion, scaffold-rearrangement and redox-neutral process coupled with an unprecedented behavior of isocyanide as a C(sp3)H–N synthon, which affords an efficient access...
An unprecedent [4 + 3] cycloaddition of furoketenimines with furocarbenoids has been disclosed for the divergent and efficient synthesis of cycloheptafuran and cycloheptapyrrole scaffolds. Zinc chloride acted as promoters for both the formation of these two transient intermediates from isocyanides and ene-yne-ketones, and the subsequent construction of seven-membered ring. Three rings and five bonds were constructed successively in this three-component one-pot domino reaction.
The formation of thermodynamically accessible metallacycle is crucial to achieve site-selective C–H bond activation. Here, we report an isocyanide-bridging C–H activation through the formation of a five-membered palladacycle. As such, a proximal C–H bond in aldehyde moiety is activated selectively. The subsequent palladium shift and intramolecular C=N bond insertion construct a valuable isoindolinone framework. Compared with conventional isocyanide-promoted C–H bond activation, both carbon and nitrogen atoms in isocyanide are engaged in new bond formations. Notably, three types of isoindolinones can be obtained selectively by variations of the reaction conditions. Mechanistic studies shed light on the reaction pathways. Moreover, the synthetic potential of current methodology is demonstrated by providing concise routes to key intermediates of indoprofen, indobufen, aristolactams, lennoxamine, and falipamil.
Multicomponent reactions (MCRs) are fundamentally different from two-component reactions in several aspects. Among the MCRs, those with isocyanides have developed into popular organic-chemical reactions in the pharmaceutical industry for the preparation of compound libraries of low-molecular druglike compounds. With a small set of starting materials, very large libraries can be built up within a short time, which can then be used for research on medicinal substances. Due to the intensive research of the last few years, many new backbone types have become accessible. MCRs are also increasingly being employed in the total synthesis of natural products. MCRs and especially MCRs with isocyanides offer many opportunities to attain new reactions and basic structures. However, this requires that the chemist learns the “language” of MCRs, something that this review wishes to stimulate.
Multicomponent reactions (MCRs) are fundamentally different from two-component reactions in several aspects. Among the MCRs, those with isocyanides have developed into popular organic-chemical reactions in the pharmaceutical industry for the preparation of compound libraries of low-molecular druglike compounds. With a small set of starting materials, very large libraries can be built up within a short time, which can then be used for research on medicinal substances. Due to the intensive research of the last few years, many new backbone types have become accessible. MCRs are also increasingly being employed in the total synthesis of natural products. MCRs and especially MCRs with isocyanides offer many opportunities to attain new reactions and basic structures. However, this requires that the chemist learns the “language” of MCRs, something that this review wishes to stimulate.
The efficacy of isocyanide reactions in the synthesis of natural or naturallike products has resulted in a renaissance of isocyanide chemistry. Now isocyanides are widely used in different branches of organic, inorganic, coordination, combinatorial and medicinal chemistry. This invaluable reference is the only book to cover the topic in such depth, presenting all aspects of synthetic isonitrile chemistry. The highly experienced and internationally renowned editor has brought together an equally distinguished team of authors who cover multicomponent reactions, isonitriles in total synthesis, isonitriles in polymer chemistry and much more.
Insertion of the isocyanides 2,6-dimethylphenyl isocyanide (DIC), teri-butyl isocyanide (TIC) and tosylmethyl isocyanide (TosMIC) into the Pd-Me bond of complexes (N̂N)Pd(Me)Cl (N̂N = 2,2′-bipyridine (bpy), 1,10-phenanthroline (phen), 2,2′-bipyrimidine (bpm)) afforded quantitatively (N̂N)Pd(C(=N-R)Me)Cl (R = 2,6-Me2C6H3, t-Bu, CH2Tosyl). The course of the reaction has been shown to proceed via the intermediates [(N̂N)Pd(CN-R)(Me)]Cl (N̂N = bpy, phen; R = 2,6-Me2C6H3, t-Bu, CH2Tosyl), which have been characterized at 250 K by NMR and IR spectroscopies and conductivity measurements. The mechanism of the insertion reaction involves substitution of the halide by the isocyanide followed by a rate-determining methyl migration to the precoordinated isocyanide. Kinetic measurements of the isocyanide insertion reaction, which provided the reaction rate constants of the isocyanide association (k1), isocyanide dissociation (k-1), and methyl migration reaction (k2), have demonstrated that the migration rate of the methyl group to the precoordinated isocyanide increases with increasing electrophilicity of the isocyanide. Methyl migration in the intermediate complexes [(N̂N)Pd(CN-R)(Me)]Cl (N̂N = bpy, phen; R = 2,6-Me2C6H3, t-Bu, CH2Tosyl) also occurs in the solid state. The complexes (N̂N)Pd(C(=N-R)Me)X (N̂N = bpy, phen; R = t-Bu, CH2Tosyl; X = Cl, Br) show a fluxional behavior due to a site exchange of the nitrogen donor atoms. Spin saturation transfer 1H NMR experiments showed that the mechanism of this process involves Pd-N bond breaking and subsequent isomerization via a Y-shaped intermediate.
The authors present and discuss those rearrangement reactions displaying certain features not emphasized in earlier chapters, including: Cope and Claisen rearrangements catalyzed by Pd complexes; skeletal rearrangements that lead to net isomerization; allylic rearrangements and homoallyl-cyclopropylcarbinyl rearrangement; and oxidative addition and oxidative complexation of Pd to OO rearrangement reactions. A collection of the Pd-catalyzed rearrangements of epoxides, epiperoxides, and enol ethers is included.
The 2,6-dimethylphenyl- and tert-butylisocyanides (DIC and TIC, respectively) react in chlorinated solvents with the allyl dimers [Pd(μ-Cl)(η3-C3H3Me2)]2 and [Pd(μ-Cl)(η3-C3H5)]2, giving the insertion products trans-[Pd(DIC)2(C═N(2,6-Me2C6H3)CH2CHCMe2)Cl], trans-[Pd(TIC)2(C═N(CMe3)CH2CHCMe2)Cl], and trans-[Pd(DIC)2(C═N(2,6-Me2C6H3)CH2CHCH2)Cl], respectively. In particular, the reaction between the complex [Pd(μ-Cl)(η3-C3H3Me2)]2 and DIC was studied in detail, and a number of different species involved in the insertion process were identified. A mechanistic network taking into account all the involved derivatives was proposed on the basis of independently measured equilibrium and rate constants.In this respect, two independent equilibria, both involving the formation of η1-allyl intermediates, were detected and the related constants determined. The formation of such intermediates bearing the η1-allyl fragment in cis position to the isocyanide is crucial when the subsequent insertion is considered. The intermediates, however, do not display the same reactivity owing to the different thermodynamic parameters governing their formation. In particular the formation of [Pd(η1-C3H3Me2)(DIC)2Cl] (MD2Cl) represents the privileged path to the product trans-[Pd(DIC)2(C═N(2,6-Me2C6H3)CH2CHCMe2)Cl] (P) when the insertion process is carried out at RT. The alternative intermediate [Pd(η1-C3H3Me2)(DIC)3]+Cl− (MD3) hardly contributes to the formation of the product P since it is disfavored by increasing the temperature.
Isocyanide bewähren sich seit langem als unersetzliche Bausteine in der modernen organischen Chemie. Die einzigartigen Eigenschaften der Isocyanogruppe machen Isocyanide für die Synthese etlicher wichtiger Klassen von Stickstoff-Heterocyclen wie Pyrrolen, Indolen oder Chinolinen besonders wertvoll. In letzter Zeit wurde eine ganze Reihe von Cocyclisierungen von Isocyaniden über Zwitterionen und radikalische Intermediate ebenso wie übergangsmetallkatalysierte Synthesen verschiedener Arten von Heterocyclen entwickelt. Methoden, die von Isocyaniden ausgehen, weisen oftmals deutliche Vorteile gegenüber alternativen Wegen auf, was oft der verbesserten Konvergenz und der Einfachheit solcher Verfahren sowie der großen Vielfalt einfach zugänglicher Isocyanide geschuldet ist. So finden Isocyanide auch in enantioselektiven Synthesen chiraler heterocyclischer Verbindungen einschließlich Naturstoffen Verwendung.
An efficient method for the synthesis of nitrogen heterocycles containing a cyclic amidine moiety has been developed. The process involves palladium-catalyzed C(sp2)H activation and isocyanide insertion starting with readily accessible ortho-heteroarene-substituted aniline derivatives under mild conditions.
Aus den Pd(O)-Isonitril-Komplexen (I) entstehen mit den Halogenverbindungen (II) die Substitutionsprodukte (III), die mit 1,5-Diazabicyclo(5,4,0)undec-5-en (DBU) zu den Keteniminen (IV) führen.
Palladium(0) catalyzed reactions of disilanes with isocyanides provide a convenient method for preparation of N-substituted bis(silyl)imines.
Insertion of isonitriles into the silicon–tin bond of organosilylstannanes is catalysed by palladium(0) to give organosilyl(N-substituted imino)stannanes.
Die lebende Polymerisation von Arylisocyaniden gelingt mit den PdPt‐Ethindiyl‐Komplexen 1 . Die Molmassenverteilung ist bei den Polymeren 2 ( n = 10) und 3 ( n = 100) sehr eng, und die gleichen Endgruppen wie im Edukt 1 garantieren den „lebenden”︁ Charakter der Polymere. Beträgt das Verhältnis von Isocyanid zu 1 nur 2: 1, kann das Produkt der Zweifach‐Insertion isoliert werden. R = Et, n Bu; Ar beispielsweise Ph, 4‐NO 2 ,C 6 H 4 . magnified image
Palladium catalyzed reactions of ternary systems involving bromobenzene, t-butyl isocyanide, and organotin compounds were found to occur giving the corresponding imines, although the catalytic efficiencies were rather low.
This communication describes a simple and versatile method for the synthesis of cyclic imino ethers and imino thioethers, in which amino-alcohol and aminothiol, respectively, were reacted with isonitrile in the presence of PdCl2 catalyst (eq 1). Thus, heterocycles such as 2-oxazolines, 2-thiazolines and 5,6-dihydro-4H-1, 3-oxazine were readily prepared in high yields by a single-step reaction. Some typical results are shown in Table I.
The reaction of [PdCl2(PPh3)2] (1) with an excess of 2,6-xylyl isocyanide (XylNC) and H2SiMePh in refluxing toluene gave a mononuclear palladium complex of a polyimino ligand, [Pd{C(NR)C(NR)C(NR)C(NR)CH(NR)}(CNR)Cl]· 1/2C6H6 (3·1/2C6H6: R = Xyl, 30%), and a novel heterobicyclic compound, 2,6-(2‘,6‘-xylyl)2-3,7-(N-2‘,6‘-xylylimino)2-4,8-(N-2‘,6‘-xylylamino)2-2,6-diazabicyclo[3.3.0]octa-4,8-diene (4a, 15%), structures of which were determined by X-ray analyses. When the reaction was carried out in the presence of triethylamine, the yield of 4a increased up to 44%. The complex 3 involves a pentaimino moiety [−C(NR){C(NR)}3CH(NR)] derived from a successive insertion of isocyanide into the palladium−hydride bond of trans-[Pd(H)Cl(PPh3)2] (2), which was generated from the reaction of 1 and H2SiMePh in situ. The pentaimino ligand attaches to the metal through the carbon atom of the α-imino group and the lone pair electron of the γ-imino nitrogen atom, resulting in a five-membered chelate ring. The reaction of 3 with XylNC in the presence of H2SiMePh afforded the heterobicyclic compound 4a. Similar treatments of 3 with 2,4,6-mesityl isocyanide (MesNC) and carbon monoxide (80 kg cm-2) in the presence of H2SiMePh gave 2,6-(2‘,6‘-xylyl)2-3-(2‘,4‘,6‘-mesitylimino)-7-(2‘,6‘-xylylimino)-4,8-(2‘,6‘-xylylamino)2-2,6-diazabicyclo[3.3.0]octa-4,8-diene (5) and 2,6-(2‘,6‘-xylyl)2-7-(2‘,6‘-xylylimino)-4,8-(2‘,6‘-xylylamino)2-2,6-diazabicyclo[3.3.0]octa-4,8-dien-3-one (6), respectively. The structure of 6 was confirmed by X-ray crystallography. When complex 3 was treated with HCCPh, a pyrrole compound, 1-(2‘,6‘-xylylamino)-2-phenyl-4-R‘-pyrrole (R‘ = C(NR){C(NR)}2CH(NR), R = Xyl) (7), was obtained. The structure of 7·C6H6 was confirmed by X-ray crystallography. Possible mechanisms for 4−7 were proposed.
The coordinative capabilities of tert-butyl isocyanide (TIC) and 2,6-dimethylphenyl isocyanide (DIC) were shown to be perfectly comparable in spite of their different steric and electronic features. As a matter of fact, when equimolar amounts of these two isocyanides are made to compete for the same coordination sites of a Pd-allyl substrate the statistical mixture of the possible products is always observed.On the contrary, the DIC proved to be much more efficient than TIC in promoting the migratory insertion of an allyl fragment. This conclusion was simply based on the analysis of the products resulting from the reaction of an appropriate Pd-allyl complex with both isocyanides simultaneously.
Palladium-catalysed coupling between aryl- or heteroaryl-bromides, alkoxides, aryloxides or thioalkoxides, and isocyanides gives aryl-imidates and -thioimidates in high yield. Amidines can be synthesised in a one-pot procedure via imidates.
The cross-coupling reaction between 9-alkyl-9-BBN derivatives, t-butylisocyanide, and haloarenes was carried out in dioxane at 50°C in the presence of K3PO4 and a catalytic amount of Pd(PPh3)4. The reaction provides alkyl aryl ketones in high yields after hydrolysis of the ketimine intermediates.
For Abstract see ChemInform Abstract in Full Text.
Catalytic condensation of amines and isonitriles can be accomplished
efficiently at 100 °C using a palladium complex catalyst, oxygen, and
iodine to give N,N-dialkylcarbodiimides.
Palladium-catalysed three component coupling of an alkenylbromide, isonitrile and an amine or alkoxide/phenoxide affords α,β-unsaturated-amidines and -imidates.
The living polymerization of aryl isocyanides has been achieved with the PdPt-ethynediyl complexes 1. The molecular weight distributions is very narrow for the polymers 2 (nBAR = 10) and 3 (nBAR = 100), and the same end groups as in complex 1 ensure the living nature of the polymerization. If the ratio of isocyanide to 1 is restricted to 2:1, a double-insertion product can be isolated. R = Et, nBu; Ar = Ph, 4-NO2C6H4 inter alia.
A palladium-catalyzed decarboxylative cyclization of gamma-methylidene-delta-valerolactones with isocyanides has been developed to afford conjugated cyclopentenimines under mild conditions. Some preliminary results toward the development of an asymmetric variant have also been described.
A convenient one-pot palladium-catalyzed cascade process for the preparation of both benzoxazoles and benzothiazoles has been developed. While these reactions proceed to give similar compounds the mechanisms governing the processes are different as are the experimental conditions employed.
A palladium-catalyzed reaction of 2-iodoarylcarbodiimide, isocyanide, and phosphite leads to 4-imino-3,4-dihydroquinazolin-2-ylphosphonates in moderate to good yields. Three bonds are formed in a one pot procedure and the tandem process includes nucleophilic attack, isocyanide insertion, and C-N coupling.
Heterocycles containing a guanidine moiety are of great importance in medicinal chemistry (Scheme 1).[1] As a result, several methods for the synthesis of these "privileged scaffolds" have been reported.[2, 3] Classical approaches, such as the addition of diamines to isothiocyanates followed by condensation and the coupling of diamines with cyanogen bromide,[2, 4] have some clear limitations, such as the availability and toxicity of reagents. Moreover, these procedures suffer from poor atom and/or step efficiency, thus making them unattractive from a sustainability point of view.
A novel and highly efficient strategy for the synthesis of isocoumarins and phthalides through a palladium (0)-catalyzed reaction incorporating tert-butyl isocyanide has been developed. This process, providing one of the simplest methods for the synthesis of this class of valuable lactones, involves two steps including cyclization reaction and simple acid hydrolysis. The methodology is tolerant of a wide range of substrates and applicable to library synthesis.
A robust route to 4-amine-benzo[b][1,4]oxazepines relying upon a palladium-catalyzed tandem reaction of o-aminophenols, bromoalkynes and isocyanides has been developed. This chemistry presumably proceeds through the migratory insertion of isocyanides into the vinyl-palladium intermediate as a key step.
The major developments of palladium-catalyzed carbonylative syntheses of heterocycles was reviewed. The application of palladium catalyzed carbonylation reactions in the synthesis of four membered lactones was first reported by Cowell and Stille in 1980. They used PdCl2(PPh3) 2 as catalyst, and the lactones were synthesized in high yields under mild conditions. Dupont and co-workers developed a Pd(OAc)2/2- PyPPh2 system for the production of various lactones from alkynols. Palladium catalyzed carbonylation of aziridines represents another convincing procedure for the synthesis of lactams. The methodologies developed by Brickner and Tsuji and their co-workers successfully avoid the use of aziridines in the preparation of lactams, but the specificity of starting materials limited the scope. Six-membered ring lactones were produced preferentially in acetonitrile using cationic palladium complexes coordinated by certain chelating diphosphines (dppb) as catalyst.
Insertion of the isocyanides 2,6-dimethylphenyl isocyanide (DIC), tert-butyl isocyanide (TIC) and tosylmethyl isocyanide (TosMIC) into the Pd−Me bond of complexes (NN)Pd(Me)Cl (NN = 2,2‘-bipyridine (bpy), 1,10-phenanthroline (phen), 2,2‘-bipyrimidine (bpm)) afforded quantitatively (NN)Pd(C(NR)Me)Cl (R = 2,6-Me2C6H3, t-Bu, CH2Tosyl). The course of the reaction has been shown to proceed via the intermediates [(NN)Pd(CN−R)(Me)]Cl (NN = bpy, phen; R = 2,6-Me2C6H3, t-Bu, CH2Tosyl), which have been characterized at 250 K by NMR and IR spectroscopies and conductivity measurements. The mechanism of the insertion reaction involves substitution of the halide by the isocyanide followed by a rate-determining methyl migration to the precoordinated isocyanide. Kinetic measurements of the isocyanide insertion reaction, which provided the reaction rate constants of the isocyanide association (k1), isocyanide dissociation (k-1), and methyl migration reaction (k2), have demonstrated that the migration rate of the methyl group to the precoordinated isocyanide increases with increasing electrophilicity of the isocyanide. Methyl migration in the intermediate complexes [(NN)Pd(CN−R)(Me)]Cl (NN = bpy, phen; R = 2,6-Me2C6H3, t-Bu, CH2Tosyl) also occurs in the solid state. The complexes (NN)Pd(C(NR)Me)X (NN = bpy, phen; R = t-Bu, CH2Tosyl; X = Cl, Br) show a fluxional behavior due to a site exchange of the nitrogen donor atoms. Spin saturation transfer 1H NMR experiments showed that the mechanism of this process involves Pd−N bond breaking and subsequent isomerization via a Y-shaped intermediate.
An exhaustive study dealing with the kinetic and mechanistic behavior of alkyl- and arylpalladium complexes bearing pyridyl−thioethers (NS−R) and quinoline−phosphines (NP) as ancillary ligands when reacting with 2,6-dimethyl isocyanide (DIC) and tosylmethyl isocyanide (TosMIC) was undertaken. In these reactions some differently substituted isocyanides insert into the palladium−carbon bond of alkyl and aryl complexes bearing mixed (NS or NP) ligands. The reactions were carried out under equimolecular conditions since such a restrictive approach allows the determination of the rate constants related to the isocyanide insertion attack. Reactions carried out under nonstoichiometric conditions were also taken into account and the reaction products characterized. Usually the formation of an inserted bis-substituted isocyanide halide derivative of palladium(II) was observed. In a particular case the formation of an imidoyl dimer was detected. The structures of the monoinserted [Pd(NSt-Bu)(C(Tol)NR2)I] (NSt-Bu = 2-(tert-butylthiomethyl)pyridine) and of the dimer [Pd(CNR2)(C(NR2)Me)Cl]2 (R2 = 2,6-Me2C6H3) were reported.
A systematic study of the insertion reactions between (P−P)Pd(Me)Cl (where P−P = dppe, dppp, dppf) and CNR (where R = 2,6-dimethylphenyl, tert-butyl) is presented. The results have demonstrated that the insertion of CNR into the Pd−Me bond is highly dependent on the nature of the chelating phosphine. For the more strained complex formed with dppe, the insertion of isocyanides is slower and multiple insertion is not observed. This is in contrast to (dppp)Pd(Me)Cl, which reacts readily with isocyanides to produce single-, double-, and multiple-inserted products. Results analogous to those of dppp have been observed for the complexes with dppf, although the reactions are more controllable, indicating a less reactive complex. In an attempt to establish some structure−reactivity correlations, structural characterizations of (dppe)Pd{C(Me)NXyl}Cl (1) and (dppp)Pd{(CNXyl)(C(Me)NXyl)}Cl (3) have been carried out. The structural parameters obtained are consistent with the observed reactivity. The reactions between (dppe)Pd{C(Me)NXyl}Cl and unsaturated (olefins and isothiocyanates) species have also been studied. While norbornadiene (a strained diolefin) inserts into the palladium−iminoacyl bond, an addition is observed when reacting 1 with isothiocyanates.
The heterodinuclear mu-ethynediyl complex Cl(R3P)2PtC=CPd(PR3)2Cl (3) reacts with aryl isocyanides in the molar ratio 1:2 to give the double-insertion product Cl(R3P)2PtC=CC(=NAr)C(=NAr)Pd(PR3)2Cl (5). Treatment of 3 with aryl isocyanides in the molar ratio 1:100 causes a multiple and successive insertion of isocyanides into the Pd-C bond of 3, leading to isocyanide polymers 7 which have a narrow distribution of molecular weight, suggesting that the reaction is a living polymerization. The living behaviors are confirmed by trace experiments using gel permeation chromatography and the syntheses of isocyanide block copolymers (9). The (mu-ethynediyl)dipalladium complex Cl(R3P)2PdC=CPd(PR3)2Cl (1) similarly produces isocyanide polymers (10), while the (mu-butadiynediyl)dipalladium complex 11 and mononuclear palladium acetylide 13 give only single-insertion products 12 and 14, respectively.
The oxidative addition of 5-methylene-1,3-dioxolan-2-ones (1) to a low-valent palladium complex and the subsequent decarboxylation has been studied as an access to oxatrimethylenemethane-palladium (OTMM-Pd) intermediates in a catalytic process. The reaction of 5,6-dimethyl-4-methylene-1,3-dioxolan-2-one (1a) with norbornene in the presence of Pd(PPh3)4 gave 3-(2-methylpropanoyl)tricyclo[3.2.1.0(2,4)]octane (3a) via addition and isomerization. In the catalytic reaction of 1a with several isonitriles, insertion of two molecules of the isonitrile into OTMM intermediate 2a took place to give 2-iminofurans 11. Similarly, the carbonate 1a reacted with aromatic isocyanates to give the corresponding oxazolidinones 12 as a result of [3 + 2] cycloaddition. The reaction of la with trimethylsilyl cyanide gave cyanated silyl enol ether 17. The zwitterionic character of OTMM-Pd seems to explain this reactivity.
The first evidence of insertion of isocyanide into M−S bond has been demonstrated. Tetrakis(triphenylphosphine)palladium [Pd(PPh3)4] catalyzes the reaction of a disulfide (ArS)2 (1) with an isocyanide ArNC (2) (Ar = 4-MeC6H4) to produce the adducts (ArS)(CNAr)m(SAr). The reactions of 1:m adducts with 2 are also catalyzed by the Pd complex to afford 1:k adducts (k ≠ m). The mechanistic study reveals that the complex Pd(SAr)2(CNAr)(PPh3) (8) is a resting state for giving 1:1 adduct and converted into 1:1 adduct 3 (m = 1) in the presence of another 1 equiv of 1. The stoichiometric reaction of 3 with Pd(PPh3)4 provides 8, but the stoichiometric oxidative addition of 1:m adducts (m = 2, 3, 4) to Pd(PPh3)4 did not give any definitive Pd(II) species. These facts reveal that both the insertion of isocyanide(s) into Pd−S bond and the reductive elimination of 1:m adduct are reversible. The study on reactivities of isocyanide and thiolate ligands on platinum, including the X-ray crystallographic analysis of the imidoyl platinum trans-Pt[(CNAr)2SAr](SAr)(PPh3)2 (21) obtained by the oxidative addition of the C−S bond of 1:2 adduct 4 (m = 2) to Pt(PPh3)4 has also been reported.
La polymerisation du 3,2,5,6-tetramethyl-1,2-diisocyanobenzene et du 3,6-bis [(trimethylsilyl)methyl]-1,2 diisocyanobenzene catalysee par PdBrMe(PPhMe 2 ) 2 donne les poly (2,3-quinoxalines) correspondantes solubles dans les solvants organiques usuels
Full details of a study on the reactions of oligosilanes with isocyanides promoted by a palladium catalyst are described. Heating a mixture of oligosilanes and excess 2,6-disubstituted aryl isocyanide in the presence of palladium(II) acetate led to the complete insertion of isocyanide into all silicon-silicon linkages, giving oligo(silylimine) derivatives. The oligo(silylimine)s have been isolated and characterized so far in the complete insertion reaction with oligosilanes up to a hexasilane. Use of the limiting amount of isocyanide permitted insertion of isocyanide into predominantly the terminal silicon-silicon linkages. The mode of the insertion reaction depends on the substituent at the silicon, e.g., tetrasilanes with phenyl groups on the internal silicon atoms favorably underwent the insertion reaction at the terminal silicon-silicon linkages, resulting in the partial insertion. The bulkiness of the ortho substituents on the aromatic isocyanide was also found to have much influence on the insertion; hence, 2,6-diisopropylphenyl isocyanide favored the partial insertion. New skeletal rearrangement of oligosilanes took place in a palladium-catalyzed reaction of substituted aryl isocyanide with tetra- and hexasilanes, forming 3,3-bis(silyl)-l-aza-2, 4-disilacyclobutane derivatives. The rearrangement, which is unique and intriguing in that the product is properly reconstituted from four fragments of the tetrasilane and two fragments of the isocyanide, was promoted in the copresence of a tert-alkyl isocyanide.
Reactions of trans square-planar complexes of palladium alkyls with isocyanides have led to the preparation of four classes of new complexes: trans-PdL2X[C(R)=NR′] (type I) (R = CH3, Ph, o-C6H4CH3; R′ = C6H11, (CH3)3C, PhCH2, Ph; X = Br, I; L = PPh3, PPh(CH3)2, P(CH3)3, P(n-C4H9)3, PPh2(C6H11)), [Pd{PPh2(CH3)}I{C(CH3)=NR′}]2 (type II) (R′ = C6H11, (CH3)3C), trans-PdL2I[(C=NC6H11)2(CH 3)] (type III) (L = PPh3, PPh2(CH3), PPh(CH3)2, P(CH3)3), and Pd[PPh2(CH3)]I[(C=NC6H11) 3(CH3)] (type IV). The type I complex (R = CH3; R′ = C6H11; X = I; L = PPh(CH3)2, P(CH3)3, P(n-C4H9)3) and the type II complex (R′ = C6H11, in the presence of PPh2(CH3)) were converted to the corresponding type III complex; the type III complex (L = PPh2(CH3)) was converted to the corresponding type IV complex, when treated with cyclohexyl isocyanide. The steric effects of ligands and the incoming isocyanide were observed in these insertion reactions. The possible insertion pathways of isocyanide into palladium-to-carbon bonds were discussed.
An unprecedented palladium-catalyzed cyanation of aromatic C-H bonds by using tertiary amine derived isocyanide as a novel cyano source was developed. Cu(TFA)(2) was used as a requisite stoichiometric oxidant. Mechanistic studies suggest that a tertiary carbon cation-based intermediate is involved following the C-N bond breakage.
A palladium-catalyzed regioselective C-H cyanation of heteroarenes was achieved using tert-butyl isocyanide as "CN" source, which provides a new and unique strategy for the preparation of (hetero)aryl nitriles. Indoles, pyrroles, and aromatic rings could be efficiently cyanated through C-H bond activation with high regioselectivity.
Synthesis of the indole skeleton was achieved using a Pd-catalyzed cascade process consisting of isocyanide insertion and benzylic C(sp(3))-H activation. It was found that slow addition of isocyanide is effective for reducing the amount of catalyst needed and Ad(2)P(n)Bu is a good ligand for C(sp(3))-H activation. The construction of the tetracyclic carbazole skeleton was also achieved by a Pd-catalyzed domino reaction incorporating alkyne insertion.
Katalyse mit Methode : Eine ganze Reihe katalytischer Palladiumsysteme für die C‐H‐Aktivierung/C‐C‐Kupplung (siehe Schema) wurde in jüngerer Zeit entwickelt. Ein besonderer Schwerpunkt ist die Pd II ‐katalysierte Kupplung von C‐H‐Bindungen mit metallorganischen Reagentien durch Pd II /Pd ⁰ ‐Katalysezyklen. Die Vielseitigkeit dieser Katalysemethode wird demonstriert, zudem werden offene Fragen sowie das Entwicklungspotenzial des Gebietes angesprochen. magnified image
In den letzten zehn Jahren wurde die palladiumkatalysierte C‐H‐Aktivierung/C‐C‐Kupplung zu einer vielversprechenden katalytischen Umwandlung entwickelt. Allerdings sind die Möglichkeiten auf diesem Gebiet bisher noch nicht so umfangreich wie bei den Kreuzkupplungen, bei denen Aryl‐ und Alkylhalogenide eingesetzt werden. Dieser Aufsatz stellt vier ausführlich untersuchte Katalysemethoden zur C‐C‐Bindungsbildung ausgehend von C‐H‐Bindungen vor: Pd II /Pd ⁰ ‐, Pd II /Pd IV ‐, Pd ⁰ /Pd II /Pd IV ‐ und Pd ⁰ /Pd II ‐Katalyse. Außerdem werden neuere Entwicklungen bei der Pd II ‐katalysierten Kupplung von C‐H‐Bindungen mit metallorganischen Reagentien durch einen Pd II /Pd ⁰ ‐Katalysezyklus vorgestellt. Ungeachtet aller bisherigen Fortschritte verbleibt es eine wichtige Aufgabe, die Vielseitigkeit und Anwendbarkeit dieser Reaktionen auf eine breitere Grundlage zu stellen.
Die selektive aerobe Oxidation organischer Verbindungen ist eines der fundamentalsten Probleme der modernen organischen Chemie. Effektive Lösungen müssen die spezifische Reaktivität und Selektivität von molekularem Sauerstoff berücksichtigen und unterschiedliche Klassen von Oxidationsreaktionen abdecken. Die Palladiumoxidasekatalyse kombiniert die Vielseitigkeit Palladium(II)-vermittelter Oxidationen organischer Substrate mit der Oxidation des reduzierten Palladium-Katalysators durch Disauerstoff und ermöglicht so einen Zugang zu einer breiten Auswahl an selektiven aeroben Oxidationsreaktionen. Neuere Ergebnisse zeigen, dass Cokatalysatoren wie Kupfer(II), Polyoxometallate und Benzochinone in der Oxidation von Palladium(0) durch molekularen Sauerstoff verzichtbar sind. Eine große Bedeutung für diese Reaktionen haben oxidativ stabile Liganden, die die Katalysatorzersetzung minimieren, die direkte Reaktion von Palladium mit Disauerstoff fördern, die Reaktivität des organischen Substrats regulieren und asymmetrische Katalysen ermöglichen.
Das Gebiet der übergangsmetallkatalysierten direkten Arylierung unter C-H-Bindungsbruch hat in den letzten Jahren eine rasante Entwicklung erfahren, was dazu führte, dass sich solche Methoden immer mehr als Alternativen zu den herkömmlichen Kreuzkupplungen mit metallorganischen Reagentien etabliert haben. Insbesondere wurden zahlreiche Palladium- und Rutheniumkatalysatoren beschrieben, welche die direkte Arylierung von (Hetero)arenen mit anspruchsvollen Reaktionspartnern ermöglichen; hierzu gehören elektrophile Arylchloride und -tosylate oder auch einfache Arene in gekreuzten dehydrierenden Arylierungen.
Um eine CO‐Gruppe reicher : (Hetero‐)Arene sind aus der industriellen Herstellung von Agrochemikalien, Farbstoffen, Pharmaka etc. nicht wegzudenken. Während der vergangenen Jahrzehnte wurden übergangsmetallkatalysierte Kupplungen von Arylhalogeniden mit Nucleophilen aller Art entwickelt. Dieser Aufsatz fasst aktuelle Fortschritte auf dem Gebiet der palladiumkatalysierten Carbonylierungen von Arylhalogeniden und ähnlichen Verbindungen zusammen (siehe Schema). magnified image
Palladiumkatalysierte Carbonylierungen von Arylhalogeniden in Gegenwart verschiedener Nucleophile haben sich seit ihrer Einführung durch Heck und Mitarbeiter im Jahr 1974 schnell weiterentwickelt, sodass heute eine Vielzahl von Palladiumkatalysatoren für unterschiedliche Carbonylierungsreaktionen verfügbar ist. Auf diesem Weg erhältliche Carbonsäurederivate, Aldehyde und Ketone sind wichtige Zwischenstufen bei der industriellen Herstellung von Farbstoffen, Pharmaka, Agrochemikalien und anderen Produkten. In diesem Aufsatz werden aktuelle Ergebnisse aus der akademischen Forschung und erste industrielle Prozesse zusammengefasst.