Cationic Palladium Research Articles

Site-Selective 1,1-Difunctionalization of Unactivated Alkenes Enabled by Cationic Palladium Catalysis.

A palladium(II)-catalyzed 1,1-difunctionalization of unactivated terminal and internal alkenes via addition of two nucleophiles was developed using a cationic palladium(II) complex. The palladacycle generated in situ as a result of a regioselective addition of a nucleophile to the alkene can readily undergo regioselective β-hydride elimination and migratory insertion with a cationic palladium catalyst. The resulting η3-π-allyl palladium(II) complex is the key intermediate that reacts with a second nucleophile to furnish the desired 1,1-difunctionalization of the alkene. Under the optimized reaction conditions, a wide range of indoles and anilines add to alkene units of 3-butenoic or 4-pentenoic acid derivatives to afford the synthetically useful γ,γ- or δ,δ-difunctionalized products with excellent regiocontrol. Furthermore, by employing internal hydroxyl or acid groups and external carbon nucleophiles, this transformation enables unsymmetric 1,1-difunctionalization to forge challenging and important oxo quaternary carbon centers. Combining experiments and DFT calculations on the mechanism of the reaction is investigated in detail.

A new cationic palladium(II) dithiocarbamate exhibits anti-inflammatory, analgesic, and antipyretic activities through inhibition of inflammatory mediators in in vivo models.

Inflammation is being a protective mechanism of the body towards the injury. However, chronic and progressive inflammation may lead to some chronic diseases. Due to the serious unwanted effects associated with available drugs, new and safe anti-inflammatory agents are still required. Therefore, the present study was designed to investigate the anti-inflammatory, analgesics, and antipyretic properties of a new compound (4-benzylpiperidine-1-carbodithioato-κ2S,S')(1,4-bis-(diphenylphosphino)butane)palladium(II)chloride monohydrate (compound-1) in albino mice models. Compound-1 was characterized by elemental analysis, FT-IR, and multinuclear NMR spectroscopy. Initially, compound-1 was evaluated for cytotoxicity, anti-inflammatory, and analgesic activities by performing MTT assay, carrageenan-, histamine-, serotonin-, and CFA-induced paw edema, mechanical hyperalgesia, thermal hyperalgesia, and mechanical allodynia (0.1, 1, and 10mg/kg, b.w). Antipyretic activity was evaluated in brewer's yeast-induced model. The pro-inflammatory cytokines were measured by using commercially available ELISA kits. Additionally, nitrite production, antioxidant enzymes, H&E staining, muscle activity and motor coordination, and kidney and liver function tests were also determined. The results demonstrated that compound-1 significantly inhibited inflammation, pain, and febrile responses in all models at a dose of 10mg/kg without effecting viability of cells in vitro at concentrations up to 100μM. Similarly, the data clearly demonstrated significant reduction in the pro-inflammatory cytokines and nitrite production while enhancing antioxidant enzymes. Furthermore, pretreatment with compound-1 did not produce any prominent side effect on kidney, liver, stomach, and muscles. These findings suggest that compound-1 has potent anti-inflammatory-, pain-, and pyrexia-relieving properties. Hence, compound-1 might be a potential candidate for the therapeutic management of chronic inflammation and pain.

C-I-Selective Cross-Coupling Enabled by a Cationic Palladium Trimer.

While there is a growing interest in harnessing synergistic effects of more than one metal in catalysis, relatively little is known beyond bimetallic systems. This report describes the straightforward access to an air-stable Pd trimer and presents unambiguous reactivity data of its privileged capability to differentiate C-I over C-Br bonds in C-C bond formations (arylation and alkylation) of polyhalogenated arenes, which typical Pd0 and PdI -PdI catalysts fail to deliver. Experimental and computational reactivity data, including the first location of a transition state for bond activation by the trimer, are presented, supporting direct trimer reactivity to be feasible.

C−I‐Selective Cross‐Coupling Enabled by a Cationic Palladium Trimer

AbstractWhile there is a growing interest in harnessing synergistic effects of more than one metal in catalysis, relatively little is known beyond bimetallic systems. This report describes the straightforward access to an air‐stable Pd trimer and presents unambiguous reactivity data of its privileged capability to differentiate C−I over C−Br bonds in C−C bond formations (arylation and alkylation) of polyhalogenated arenes, which typical Pd0 and PdI‐PdI catalysts fail to deliver. Experimental and computational reactivity data, including the first location of a transition state for bond activation by the trimer, are presented, supporting direct trimer reactivity to be feasible.

Bidentate Iminophosphorane-NHC Ligand Derived from the Imidazo[1,5-a]pyridin-3-ylidene Scaffold

The synthesis of the bifunctional iminophosphorane-NHC (1) based on the imidazo[1,5-a]pyridin-3-ylidene (IPy) platform is reported. Its imidazo[1,5-a]pyridinium salt precursor [1·H](X) was readily obtained by an efficient three-component coupling reaction between 5-bromoimidazo[1,5-a]pyridinium bromide, sodium azide, and triphenylphosphine according to a SNAr/Staudinger reaction sequence. The stable free carbene 1 was generated by deprotonation of [1·H](X) with potassium bis(trimethylsilyl)amide, and its coordination ability toward various transition-metals was evaluated, either upon direct metalation of the free carbene or by transmetalation from a silver(I) NHC complex. While the ligand 1 is singly bounded through the carbene carbon atom in the latter complex, it behaves as a chelating bidentate ligand in all other complexes that were prepared, including the cationic and neutral palladium(II) complexes [Pd(allyl)(κ2C,N -1)](OTf) ([5](OTf)) and [PdCl2(κ2C,N -1)] (7), and the cationic rhodium(I) complexes...

Polymerization of phenylacetylene by cationic acetylacetonate palladium complexes

A series of cationic acetylacetonate palladium complexes were demonstrated to be active for the polymerization and oligomerization of phenylacetylene. Catalyst screening and optimization have determined the superior activity of complex [(acac)Pd(TOMPP)2]BF4 (TOMPP – tris(2-methoxyphenyl)phosphine) for the stereospecific polymerization of phenylacetylene in non-coordinating solvents as well as in an aqueous emulsion. Catalyst turnover frequencies of 100–160 h−1 were observed (Mw = (10–27)·104 with PDI = 1.7–2.3, cis double bond content in PPA up to 95%). The effect of temperature, solvent nature, and the use of cocatalyst, BF3·OEt2, have been studied.

Non-Selective Dimerization of Vinyl Silanes by the Putative (Phenanthroline)PdMe Cation to 1,4-Bis(trialkoxysilyl)butenes

Activation of the dialkylpalladium complex (phen)Pd(CH3)2 (phen = 1,10-phenanthroline) with B(C6F5)3 affords a competent catalyst for the dimerization of vinyl silanes. All organic products of the catalytic dimerization of trialkoxyvinylsilanes were characterized by in situ NMR spectroscopy and GC–MS. The putative palladium cation was characterized by NMR spectroscopy. Upon activation, the palladium complex generated products in moderate yield (60–70%) and selectivity (~60:40, dimer:disproportionation products).

Olefin Dimerization and Isomerization Catalyzed by Pyridylidene Amide Palladium Complexes

A series of cationic palladium complexes [Pd(N∧N′)Me(NCMe)]+ was synthesized, comprising three different N∧N′-bidentate coordinating pyridyl–pyridylidene amide (PYA) ligands with different electronic and structural properties depending on the PYA position (o-, m-, and p-PYA). Structural investigation in solution revealed cis/trans isomeric ratios that correlate with the donor properties of the PYA ligand, with the highest cis ratios for the complex having the most donating o-PYA ligand and lowest ratios for that with the weakest donor p-PYA system. The catalytic activity of the cationic complexes [Pd(N∧N′)Me(NCMe)]+ in alkene insertion and dimerization showed a strong correlation with the ligand setting. While complexes bearing more electron donating m- and o-PYA ligands produced butenes within 60 and 30 min, respectively, the p-PYA complex was much slower and only reached 50% conversion of ethylene within 2 h. Likewise, insertion of methyl acrylate as a polar monomer was more efficient with stronger dono...

Cationic Chiral Pd-Catalyzed "Acetylenic" Diels-Alder Reaction: Computational Analysis of Reversal in Enantioselectivity.

The highly enantioselective Diels-Alder reaction of acetylenic dienophiles is shown to be effectively catalyzed by cationic chiral palladium complexes. Not only the degree but also the sense of enantioselectivity critically depends on the steric demand of ligands. Computational analyses indicate that the steric demand does not affect the endo/exo-selectivity but the enantioface selectivity of dienes.

Light as a Catalytic Switch for Block Copolymer Architectures: Metal–Organic Insertion/Light Initiated Radical (MILRad) Polymerization

We detail a polymer synthetic methodology that merges the techniques of insertion and radical polymerization methods into a single organometallic catalyst. This metal–organic insertion/light initiated radical (MILRad) polymerization technique proves successful at polymerizing methyl acrylate (MA) and hexene, using light as a critical stimulus to activate the dormant photoresponsive nature of the insertion catalyst. In this study, we describe a novel approach that uses visible light (460 nm) to switch the catalytic activity of a cationic palladium catalyst from an insertion route to a radical process when desired. We discovered that in a mixture of MA and hexene one monomer can be selectively polymerized using light and dark cycles, respectively. As a result, this polymerization process enables the copolymerization of MA and hexene to create homo- and block copolymer architectures facilitated solely by visible light. In this work, we show the synthesis of MA homopolymers in molecular weight ranges (Mn 50–4...

Water-soluble SNS cationic palladium(II) complexes and their Suzuki-Miyaura cross-coupling reactions in aqueous medium.

Unlike their SCS analogues, SNS pincer complexes are poorly studied for their use in coupling reactions. Accordingly, a series of water soluble cationic Pd(II) SNS pincer complexes have been successfully synthesised and investigated in detail for their catalytic activity in Suzuki–Miyaura coupling reactions. By using only 0.5 mol % loading of the complexes, the coupling of inactivated aryl bromides and activated aryl chlorides with various boronic acids in water was achieved in excellent yields and the catalysts were found to be reusable for three cycles without a significant loss of activity. The investigation of the mechanism of the reaction revealed that a Pd(II) to Pd(IV) route is the more likely pathway which was further supported by computational studies.

Enantioselective, Noncovalent, Substrate-Directable Heck-Matsuda and Oxidative Heck Arylations of Unactivated Five-Membered Carbocyclic Olefins.

Highly diastereo- and enantioselective, noncovalent, substrate-directable Heck desymmetrizations of cyclopentenyl olefins containing hydroxymethyl and carboxylate functional groups are presented. These conformationally unbiased cyclic olefins underwent effective arylations in yields of up to 97 %, diastereoselectivity up to >20:1, and enantiomeric excesses of up to 99 %. Noncovalent directing effects were shown to be prevalent in both Heck-Matsuda and oxidative Heck reactions, allowing the preferential formation of cis-substituted aryl cyclopentenes containing two stereocenters, including quaternary stereocenters. These results further validate the internal out-of-coordination-sphere ion-dipole interaction concept directing the reaction diastereoselectivity to the cis-Heck product. This approach is complementary to existing methods using bis-phosphine monoxide ligands to give the opposite trans-diastereoisomer. The applicability of the method is showcased by the straightforward synthesis of a potent phosphodiesterase 4 inhibitor in a diastereo- and enantioselective manner. The reaction is operationally simple and has broad scope with regard to the nature of the arenediazonium salt and boronic acid employed. The mechanism and origin of stereoselectivity were investigated with control experiments and DFT calculations that fully supported the stabilizing internal out-of-coordination-sphere ion-dipole interaction between the resident functional group and cationic palladium.

Breaking the Base Barrier: An Electron-Deficient Palladium Catalyst Enables the Use of a Common Soluble Base in C-N Coupling.

Due to the low intrinsic acidity of amines, palladium-catalyzed C-N cross-coupling has been plagued continuously by the necessity to employ strong, inorganic, or insoluble bases. To surmount the many practical obstacles associated with these reagents, we utilized a commercially available dialkyl triarylmonophosphine-supported palladium catalyst that facilitates a broad range of C-N coupling reactions in the presence of weak, soluble bases. The mild and general reaction conditions show extraordinary tolerance for even highly base-sensitive functional groups. Additionally, insightful heteronuclear NMR studies using 15N-labeled amine complexes provide evidence for the key acidifying effect of the cationic palladium center.

Phenylacetylene polymerisation mediated by cationic cyclometallated palladium(ii) complexes bearing benzylidene 2,6-diisopropylphenylamine and its derivatives as ligands.

A series of novel cationic palladacycle complexes bearing benzylidene-2,6-diisopropylphenylamine derivatives as ligands and with the general formula [Pd(MeCN)(L)(R-C6H3)CH[double bond, length as m-dash]N{2,6-iPr2-C6H3}][B(3,5-(CF3)2-C6H3)] (R = H, Cl, Br, F, OMe and L = 1,3,5-triaza-7-phosphaadamantane (PTA), tricyclohexylphosphine (PCy3) and triphenylphosphine (PPh3)) were prepared and characterized by a range of analytical techniques. These cationic palladacycle complexes were found to be active precatalysts for the polymerisation of phenylacetylene. The meta-substituent on the cyclometallated ring was found to have a marked effect on the catalyst performance in that complexes, which contained electron-withdrawing substituents, were found to be the most active in the polymerisation process. Furthermore, increasing the steric bulk of the phosphine ligand led to the production of higher molecular weight polyphenylacetylenes (PPA). Polymerisation reactions performed at 25 °C gave a mixture of both cis-transoidal and trans-cisoidal PPA while trans-cisoidal PPA was selectively produced at elevated temperatures (60 °C). Preliminary mechanistic studies demonstrated that polymerisation proceeds via dissociation of the C,N-chelating ligand, and involves the formation of an iminium cationic fragment.

Cationic Palladium(II)-Catalyzed Reductive Cyclization of Alkynyl Cyclohexadienones.

A cationic palladium(II)-catalyzed reductive cyclization of cyclohexadienone-containing 1,6-enynes by using ethanol as a hydrogen donor and solvent was successfully developed. This procedure offers convenient access to cyclohexenone-annulated heterocycles under mild reaction conditions. The reaction was initiated by hydropalladation of the alkyne and was quenched by addition of the intramolecular conjugate alkene. This possible mechanism was preliminarily demonstrated by deuterium-labeling experiments.

Cationic Palladium(II) Complexes for Catalytic Wacker‐Type Oxidation of Styrenes to Ketones Using O2 as the Sole Oxidant

A series of new cationic palladium(II) complexes were prepared and studied for their ability to catalyze the Wacker‐type oxidation of styrenes to their corresponding acetophenones using O2 as the sole oxidant. Catalysts are active at room temperature and the study highlights the importance of solvent choice and the need for ligand development in improving catalyst performance.

Cationic acetylacetonate palladium complexes/boron trifluoride etherate catalyst systems for polymerization of 5-methoxycarbonylnorbornene

A simple protocol using cationic acetylacetonate palladium complexes with mono-/bidentate phosphine ligands activated with BF3·OEt2 as in situ-formed catalyst for polymerization of endo/exo mixture of 5-methoxycarbonylnorbornene (activity up to 1.1·104gmol−1h−1) or 5-phenylnorbornene (7.2·105gmol−1h−1), and norbornene (3.3·108gmol−1h−1) have been developed. It was observed that the ligands nature strongly influence the catalytic activity. The catalyst system Pd(II)/BF3·OEt2 was also active for the copolymerization of norbornene with 5-methoxycarbonylnorbornene. DFT calculations of isomers upon single insertion of 5-methoxycarbonylnorbornene into PdH bond and NMR/FTIR studies for pre-catalyst activation mechanism were performed.

Cationic NCN Palladium(II) Pincer Complexes of 5-tert-Butyl-1,3-bis(N-substituted benzimidazol-2′-yl)benzenes: Synthesis, Structure, and Pd···Pd Metallophilic Interaction

The NCN palladium(II) pincer complex [Benzoyl(N∧C∧N)PdBr] (16) was synthesized by the oxidative addition of Benzoyl(N∧C∧N)Br to Pd(dba)2 in 85% yield [(N∧C∧N) = 5-tert-butyl-1,3-bis(N-substituted benzimidazol-2′-yl)phenyl)]. Then treatment of complex 16 with KI yielded the iodopalladium complex [Benzoyl(N∧C∧N)PdI] (17) in 92% yield. Furthermore, a series of cationic palladium(II) complexes, including [Benzoyl(N∧C∧N)Pd(MeCN)]+[BF4]− (18), [Benzoyl(N∧C∧N)Pd(MeCN)]+[SbF6]− (19), and [Benzoyl(N∧C∧N)Pd(OTf)] (20), were prepared in 68–79% yields by the reaction of the neutral palladium(II) complex (16) with AgBF4, AgSbF6, and AgOTf, respectively. Similarly, previously synthesized Tosyl(N∧C∧N)PdBr [5-tert-butyl-1,3-bis(N-tosylbenzimidazol-2′-yl)phenyl]palladium bromide (5b) was treated with AgSO3CF3 and AgSbF6 to afford cationic palladium(II) complexes [Tosyl(N∧C∧N)Pd(OTf)] (21) and [Tosyl(N∧C∧N)Pd(MeCN)]+[SbF6]− (22) in 41 and 61% yields, respectively. 5-tert-Butyl-1,3-bis[{(N-tosylbenzimidazol-2′-yl)phenyl}pal...

Synthesis, characterization, and catalytic ethylene oligomerization of pyridine-imine palladium complexes

Two neutral five-membered pyridine-imine palladium complexes with the bulky dibenzhydryl (CH(Ph)2) substituted aniline were synthesized and fully characterized by nuclear magnetic resonance (NMR) and X-ray crystal diffraction. Well-defined cationic palladium complexes were further obtained by treatment of chloromethylpalladium complexes with sodium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (NaBArF) in CH3CN. Cationic palladium complexes were capable of catalyzing ethylene oligomerization without any cocatalysts. The influences of catalyst structure, reaction temperature, and ethylene pressure on ethylene oligomerization were studied in detail. The introduction of bulky benzhydryl (CH(Ph)2) on the ortho position of the aniline moiety enhanced catalytic activity, thermal stability of the catalyst, and molecular weight of the obtained products. Highly branched oligomers with molecular weights of 600–800 g/mol and narrow polydispersities (1.03–1.12) were produced.

Palladium(II) complexes bearing mixed N^N^X (X = O and S) tridentate ligands as pre-catalysts for the methoxycarbonylation of selected 1-alkenes

The methoxycarbonylation of selected 1-alkenes catalyzed by various neutral and cationic palladium(II) complexes, containing mixed N^N^X (X = O and S) tridentate ligands 2-[(3,5-dimethyl-1H-pyrazol-1-yl)methyl]-6-(phenoxymethyl)pyridine (L1), 2-[(3,5-di-tert-butyl-1H-pyrazol-1-yl)methyl]-6-(phenoxymethyl)pyridine (L2), 2-[(3,5-dimethyl-1H-pyrazol-1-yl)methyl]-6-(phenylthiomethyl)pyridine (L3), 2-[(3,5-di-tert-butyl-1H-pyrazol-1-yl)methyl]-6-(phenylthiomethyl)pyridine (L4), has been investigated. Neutral complexes, [(ĸ2-L1)Pd(CH3)(Cl)] (1a), [(ĸ2-L2)Pd(CH3)(Cl)] (2a), [(ĸ2-L3)Pd(CH3)(Cl)] (3a), [(ĸ2-L4)Pd(CH3)(Cl)] (4a), and the salts, [(ĸ3-L3)Pd(CH3)][BAr4F] (3c) and [(ĸ3-L4)Pd(CH3)][BAr4F] (4c), underwent complete decomposition during the reaction to palladium black and showed no catalytic activity. However, the addition of PPh3 to the reaction dramatically increased the catalytic activity. On the other hand, the salts, [(ĸ2-L1)Pd(CH3)(PPh3)][BAr4F] (1b), [(ĸ2-L2)Pd(CH3)(PPh3)][BAr4F] (2b), [(ĸ2-L3)Pd(CH3)(PPh3)][BAr4F] (3b) and [(ĸ2-L4)Pd(CH3)(PPh3)][BAr4F] (4b), showed good conversion of the selected olefins to branched and linear esters without PPh3. Addition of PPh3 to reactions with 1b-4b significantly improved catalytic activity. All decomposition of complexes led to the formation of the known palladium complexes, [Pd(PPh3)2(Cl)(CH3)] and [Pd(PPh3)2Cl2]. The decomposition of all palladium complexes could be followed by NMR studies and [Pd(PPh3)2Cl2] could be isolated from the crude methoxycarbonylation reaction.