Palladium‐Catalyzed Intramolecular Reductive Cross‐Coupling of Csp2Csp3 Bond Formation

A Pd‐catalyzed efficient reductive cross‐coupling reaction without metallic reductant to construct a Csp²?Csp³ bond has been reported. A Pd^IV complex was proposed to be a key intermediate, which subsequently went through double oxidative addition and double reductive elimination to produce the cross‐coupling products by involving Pd^0/II/IV in one transformation. The oxidative addition from Pd^II to Pd^IV was partially demonstrated to be a radical process by self‐oxidation of substrate without additional oxidants. Furthermore, the solvent was proved to be the reductant for this transformation through XPS analysis.     

Pincer‐Type Heck Catalysts and Mechanisms Based on PdIV Intermediates: A Computational Study

Pincer‐type palladium complexes are among the most active Heck catalysts. Due to their exceptionally high thermal stability and the fact that they contain Pd^II centers, controversial Pd^II/Pd^IV cycles have been often proposed as potential catalytic mechanisms. However, pincer‐type Pd^IV intermediates have never been experimentally observed, and computational studies to support the proposed Pd^II/Pd^IV mechanisms with pincer‐type catalysts have never been carried out. In this computational study the feasibility of potential catalytic cycles involving Pd^IV intermediates was explored. Density functional calculations were performed on experimentally applied aminophosphine‐, phosphine‐, and phosphite‐based pincer‐type Heck catalysts with styrene and phenyl bromide as substrates and (E)‐stilbene as coupling product. The potential‐energy surfaces were calculated in dimethylformamide (DMF) as solvent and demonstrate that Pd^II/Pd^IV mechanisms are thermally accessible and thus a true alternative to formation of palladium nanoparticles. Initial reaction steps of the lowest energy path of the catalytic cycle of the Heck reaction include dissociation of the chloride ligands from the neutral pincer complexes [{2,6‐C₆H₃(XPR₂)₂}Pd(Cl)] [X=NH, R=piperidinyl ( 1 a ); X=O, R=piperidinyl ( 1 b ); X=O, R=iPr ( 1 c ); X=CH₂, R=iPr ( 1 d )] to yield cationic, three‐coordinate, T‐shaped 14e^? palladium intermediates of type [{2,6‐C₆H₃(XPR₂)₂}Pd]⁺ ( 2 ). An alternative reaction path to generate complexes of type 2 (relevant for electron‐poor pincer complexes) includes initial coordination of styrene to 1 to yield styrene adducts [{2,6‐C₆H₃(XPR₂)₂}Pd(Cl)(CH₂?CHPh)] ( 4 ) and consecutive dissociation of the chloride ligand to yield cationic square‐planar styrene complexes [{2,6‐C₆H₃(XPR₂)₂}Pd(CH₂?CHPh)]⁺ ( 6 ) and styrene. Cationic styrene adducts of type 6 were additionally found to be the resting states of the catalytic reaction. However, oxidative addition of phenyl bromide to 2 result in pentacoordinate Pd^IV complexes of type [{2,6‐C₆H₃(XPR₂)₂}Pd(Br)(C₆H₅)]⁺ ( 11 ), which subsequently coordinate styrene (in trans position relative to the phenyl unit of the pincer cores) to yield hexacoordinate phenyl styrene complexes [{2,6‐C₆H₃(XPR₂)₂}Pd(Br)(C₆H₅)(CH₂?CHPh)]⁺ ( 12 ). Migration of the phenyl ligand to the olefinic bond gives cationic, pentacoordinate phenylethenyl complexes [{2,6‐C₆H₃(XPR₂)₂}Pd(Br)(CHPhCH₂Ph)]⁺ ( 13 ). Subsequent β‐hydride elimination induces direct HBr liberation to yield cationic, square‐planar (E)‐stilbene complexes with general formula [{2,6‐C₆H₃(XPR₂)₂}Pd(CHPh?CHPh)]⁺ ( 14 ). Subsequent liberation of (E)‐stilbene closes the catalytic cycle.     

Is PdII‐Promoted σ‐Bond Metathesis Mechanism Operative for the PdPEPPSI Complex‐Catalyzed Amination of Chlorobenzene with Aniline? Experiment and Theory

Reduction of the Pd?PEPPSI precatalyst to a Pd⁰ species is generally thought to be essential to drive Buchwald–Hartwig amination reactions through the well‐ documented Pd⁰/Pd^II catalytic cycle and little attention has been paid to other possible mechanisms. Considered here is the Pd?PEPPSI‐catalyzed aryl amination of chlorobenzene with aniline. A neat reaction system was used in new experiments, from which the potentially reductive roles of the solvent and labile ligand of the PEPPSI complex in leading to Pd⁰ species are ruled out. Computational results demonstrate that anilido‐containing Pd^II intermediates involving σ‐bond metathesis in pathways leading to the diphenylamine product have relatively low barriers. Such pathways are more favorable energetically than the corresponding reductive elimination reactions resulting in Pd⁰ species and other putative routes, such as the Pd^II/Pd^IV mechanism, single electron transfer mechanism, and halide atom transfer mechanism. In some special cases, if reactants/additives are inadequate to reduce a Pd^II precatalyst, a Pd^II‐involved σ‐bond metathesis mechanism might be feasible to drive the Buchwald–Hartwig amination reactions.     

A Preliminary Study of Diastereoselectivity in the PdII‐Catalyzed C(sp3)‐H Alkoxylation of Cyclic Systems

Primary mechanism of a Pd^II‐catalyzed 8‐aminoquinoline‐directed C?H alkoxylation was investigated. It was understood that the Pd^II‐catalyzed C(sp³)?O bond formation proceeded through a concerted reductive elimination from the Pd^IV intermediate in the cyclic system. Deuteration experiments and related computational studies elucidate that intrinsic conformation determined the diastereoselectivity of the Pd^II‐catalyzed C?H alkoxylation of cyclic carboxylic acids.     

Palladium‐Catalyzed Cascade CH Trifluoroethylation of Aryl Iodides and Heck Reaction: Efficient Synthesis of ortho‐Trifluoroethylstyrenes

A palladium‐catalyzed selective C? H bond trifluoroethylation of aryl iodides has been explored. The reaction allows for the efficient synthesis of a variety of ortho‐trifluoroethyl‐substituted styrenes. Preliminary mechanistic studies indicate that the reaction might involve a key Pd^IV intermediate, which is generated through the rate‐determining oxidative addition of CF₃CH₂I to a palladacycle; the bulky nature of CF₃CH₂I influences the reactivity. Reductive elimination from the Pd^IV complex then leads to the formation of the aryl–CH₂CF₃ bond.     

Metal‐binding Sites of N‐Acetylneuraminic Acid

Sialic acid represents a group of thirty derivates of neuraminic acid with various substituents at the amino residue and the alcoholic hydroxy groups. We analysed the behaviour of the tetracoordinated metal ions palladium(II) and silicon(IV) against the most important derivative N‐acetylneuraminic acid (NANA). The molecular structures were assigned by a combined ¹H, ¹³C and ²⁹Si NMR‐spectroscopic approach. Despite the presence of many different functional groups, the coordination chemistry of NANA with Pd^II follows established rules. Coordination via the N‐acetyl‐group – sterically impossible with Pd^II – was realised with Si^IV.     

Employing Aryl‐Linked Bis‐mesoionic Carbenes as a Pincer‐Type Platform to Access Ambient‐Stable Palladium(IV) Complexes

The study of palladium(IV) species has great implications for Pd^II/Pd^IV‐mediated catalysis. However, most of the Pd^IV complexes rapidly decompose under ambient conditions, which makes the isolation, characterization and further reactivity study very challenging. The reported ancillary ligand platforms to stabilize Pd^IV species are dominated by chelating N‐donors such as bipyridines. In this work, we present two Pd^IV complexes with scarcely used C‐donors as the supporting platform. The anionic aryl donor and MIC (MIC=mesoionic carbene) are combined in a [CC′C]‐type pincer framework to access a series of ambient‐stable Pd^IV tris(halido) complexes. Their synthesis, solid‐state structures, stability, and reactivity are presented. To the best of our knowledge, the work presented herein reports the first isolated Pd^IV–MIC as well as the first Pd^IV carbene‐based aryl pincer.     

Stability and Unimolecular Reactivity of Palladate(II) Complexes [LnPdR3]− (L=Phosphine,R=Organyl,n=0 and 1)

The reduction of Pd^II precatalysts to catalytically active Pd⁰ species is a key step in many palladium‐mediated cross‐coupling reactions. Besides phosphines, the stoichiometrically used organometallic reagents can afford this reduction, but do so in a poorly understood way. To elucidate the mechanism of this reaction, we have treated solutions of Pd(OAc)₂ and a phosphine ligand L in tetrahydrofuran with RMgCl (R=Ph, Bn, Bu) as well as other organometallic reagents. Analysis of these model systems by electrospray‐ ionization mass spectrometry found palladate(II) complexes [L_nPdR₃]^? (n=0 and 1), thus pointing to the occurrence of transmetallation reactions. Upon gas‐phase fragmentation, the [L_nPdR₃]^? anions preferentially underwent a reductive elimination to yield Pd⁰ species. The sequence of the transmetallation and reductive elimination, thus, constitutes a feasible mechanism for the reduction of the Pd(OAc)₂ precatalyst. Other species of interest observed include the Pd^IV complex [PdBn₅]^?, which did not fragment via a reductive elimination but lost BnH instead.     

Mechanistic Insights into Palladium‐Catalyzed Silylation of Aryl Iodides with Hydrosilanes through a DFT Study

The catalytic cycles of palladium‐catalyzed silylation of aryl iodides, which are initiated by oxidative addition of hydrosilane or aryl iodide through three different mechanisms characterized by intermediates R₃Si−Pd^II−H (Cycle A), Ar−Pd^II−I (Cycle B), and Pd^IV (Cycle C), have been explored in detail by hybrid DFT. Calculations suggest that the chemical selectivity and reactivity of the reaction depend on the ligation state of the catalyst and specific reaction conditions, including feeding order of substrates and the presence of base. For less bulky biligated catalyst, Cycle C is energetically favored over Cycle A, through which the silylation process is slightly favored over the reduction process. Interestingly, for bulky monoligated catalyst, Cycle B is energetically more favored over generally accepted Cycle A, in which the silylation channel is slightly disfavored in comparison to that of the reduction channel. Moreover, the inclusion of base in this channel allows the silylated product become dominant. These findings offer a good explanation for the complex experimental observations. Designing a reaction process that allows the oxidative addition of palladium(0) complex to aryl iodide to occur prior to that with hydrosilane is thus suggested to improve the reactivity and chemoselectivity for the silylated product by encouraging the catalytic cycle to proceed through Cycles B (monoligated Pd⁰ catalyst) or C (biligated Pd⁰ catalyst), instead of Cycle A.     

Photolysis and Thermolysis of Platinum(IV) 2,2′‐Bipyridine Complexes Lead to Identical Platinum(II)–DNA Adducts

Two Pt^IV and two Pt^II complexes containing a 2,2′‐bipyridine ligand were treated with a short DNA oligonucleotide under light irradiation at 37 °C or in the dark at 37 and 50 °C. Photolysis and thermolysis of the Pt^IV complexes led to spontaneous reduction of the Pt^IV to the corresponding Pt^II complexes and to binding of Pt^II 2,2′‐bipyridine complexes to N7 of guanine. When the reduction product was [Pt(bpy)Cl₂], formation of bis‐oligonucleotide adducts was observed, whereas [Pt(bpy)(MeNH₂)Cl]⁺ gave monoadducts, with chloride ligands substituted in both cases. Neither in the dark nor under light irradiation was the reductive elimination process of these Pt^IV complexes accompanied by oxidative DNA damage. This work raises the question of the stability of photoactivatable Pt^IV complexes toward moderate heating conditions.     

Site‐Selective Ligand Exchange on a Heteroleptic TiIV Complex Towards Stepwise Multicomponent Self‐Assembly

A series of heteroleptic [Ti 1 ₂X]^? complexes have been selectively constructed from a mixture of Ti^IV ions, a pyridyl catechol ligand (H₂ 1 ; H₂ 1 =4‐(3‐pyridyl)catechol), and various bidentate ligands (HX) in the presence of a weak base, in addition to a previously reported [Ti 1 ₂(acac)]^? (acac=acetylacetonate) complex. Comparative studies of these Ti^IV complexes revealed that [Ti 1 ₂(trop)]^? (trop=tropolonate) is much more stable than the [Ti 1 ₂(acac)]^? complex, which allows the replacement of acac with trop on the [Ti 1 ₂(acac)]^? complex. This Ti^IV‐centered site‐selective ligand exchange reaction also takes place on a heteronuclear Pd^II? Ti^IV ring complex with the preservation of the Pd^II‐centered coordination structures. Intra‐ and intermolecular linking between two Ti^IV centers with a flexible or a rigid bis‐tropolone bridging ligand provided a tetranuclear and an octanuclear Pd^II? Ti^IV complex, respectively. These higher‐order structures could be efficiently constructed only through a stepwise synthetic route.     

Palladium‐Catalyzed Regioselective Diarylation of o‐Carboranes By Direct Cage B−H Activation

Palladium‐catalyzed intermolecular coupling of o‐carborane with aromatics by direct cage B?H bond activation has been achieved, leading to the synthesis of a series of cage B(4,5)‐diarylated‐o‐carboranes in high yields with excellent regioselectivity. Traceless directing group ‐COOH plays a crucial role for site‐ and di‐selectivity of such intermolecular coupling reaction. A Pd^II–Pd^IV–Pd^II catalytic cycle is proposed to be responsible for the stepwise arylation.     

Solvent‐Enhanced Diastereo‐ and Regioselectivity in the PdII‐Catalyzed Synthesis of Six‐ and Eight‐Membered Heterocycles via cis‐Aminopalladation

The Pd^II‐catalyzed intramolecular oxidative cyclization of tosyl‐protected cis‐ and trans‐N‐allyl‐2‐aminocyclohexanecarboxamides was examined, and efficient syntheses of cyclohexane‐fused pyrimidin‐4‐ones and 1,5‐diazocin‐6‐ones were developed. In the course of the research, a marked solvent effect was observed on both the regio‐ and diastereoselectivity. Additionally, a novel Pd^II‐mediated domino oxidation, oxidative amination reaction was discovered. Our experimental and theoretical findings suggest that the reactions proceed via a cis‐aminopalladation mechanism.     

Mechanistic Study on the Palladium(II)‐Catalyzed Synthesis of 2,3‐Disubstituted Indoles Under Aerobic Conditions: Anion Effects and the Development of a Low‐Catalyst‐Loading Process

As a result of detailed mechanistic and kinetic studies, we have proposed that PdX₂‐catalyzed oxidative coupling of o‐alkynylanilines 1 with terminal alkynes 2 under aerobic conditions is initiated by aminopalladation of 1 followed by ligand exchange of the resulting σ‐indolylpalladium(II) complex with 2 , reductive elimination and N‐demethylation. Side reactions associated with intermediates on the way to 2,3‐disubstituted indoles 3 were identified, and the roles of acetate and iodide in channeling the reaction towards the desired product were established. Based on kinetic and spectroscopic studies, the soluble iodide‐ligated Pd⁰ species was proposed to be the resting state of the catalyst and its oxidation to active Pd^II species was the turnover‐limiting step. Catalytic conditions with low loading of Pd(OAc)₂ (0.0005 to 0.001 equiv) were subsequently developed.     

Providing Support in Favor of the Existence of a PdII/PdIV Catalytic Cycle in a Heck‐Type Reaction

The complex [Pd(O,N,C‐L)(OAc)], in which L is a monoanionic pincer ligand derived from 2,6‐diacetylpyridine, reacts with 2‐iodobenzoic acid at room temperature to afford the very stable pair of Pd^IV complexes (OC‐6‐54)‐ and (OC‐6‐26)‐[Pd(O,N,C‐L)(O,C‐C₆H₄CO₂‐2)I] (1.5:1 molar ratio, at ?55 °C). These complexes and the Pd^II species [Pd(O,N,C‐L)(OX)] and [Pd(O,N,C‐L′)(NCMe)]ClO₄, (X=MeC(O) or ClO₃, L′=another monoanionic pincer ligand derived from 2,6‐diacetylpyridine), are precatalysts for the arylation of CH₂?CHR (R?CO₂Me, CO₂Et, Ph) using IC₆H₄CO₂H‐2 and AgClO₄. These catalytic reactions have been studied and a tentative mechanism is proposed. The presence of two Pd^IV complexes was detected by ESI(+)‐MS during the catalytic process. All the data obtained strongly support a Pd^II/Pd^IV catalytic cycle.     

Carboxymethylcellulose‐supported palladium nanoparticles generated in situ from palladium(II) carboxymethylcellulose as an efficient and reusable catalyst for ligand‐ and base‐free Heck–Matsuda and Suzuki–Miyaura couplings

A novel palladium(II) carboxymethylcellulose (CMC‐Pd^II) was prepared by direct metathesis from sodium carboxymethylcellulose and PdCl₂ in aqueous solution. Its catalytic activities were explored for Heck–Matsuda reactions of aryldiazonium tetrafluoroborate with olefins, and Suzuki–Miyaura couplings of aryldiazonium tetrafluoroborate with arylboronic acid. Both reactions proceeded at room temperature in water or aqueous ethanol media without the presence of any ligand or base, to provide the corresponding cross‐coupling products in good to excellent yields under atmospheric conditions. The CMC‐Pd^II and carboxymethylcellulose‐supported palladium nanoparticles (CMC‐Pd⁰) formed in situ in the reactions were characterized using Fourier transform infrared spectroscopy, X‐ray diffraction, inductively coupled plasma atomic emission spectrometry, and scanning and transmission electron microscopies. The homogeneous nature of the CMC‐Pd⁰ catalyst was confirmed via Hg(0) and CS₂ poisoning tests. Moreover, the CMC‐Pd⁰ catalyst could be conveniently recovered by simple filtration and reused for at least ten cycles in Suzuki–Miyaura reactions without apparently losing its catalytic activity. The catalytic system not only overcomes the basic drawbacks of homogeneous catalyst recovery and reuse but also avoids the need to fabricate palladium nanoparticles in advance. Copyright © 2015 John Wiley & Sons, Ltd.     

Hydroxypalladation Precedes the Rate‐Determining Step in the Wacker Oxidation of Ethene

The complete reaction mechanism and kinetics of the Wacker oxidation of ethene in water under low [Cl^?], [Pd^II], and [Cu^II] conditions are investigated in this work by using ab initio molecular dynamics. These extensive simulations shed light on the molecular details of the associated individual steps, along two different reaction routes, starting from a series of ligand‐exchange processes in the catalyst precursor PdCl₄^2? to the final aldehyde‐formation step and the reduction of Pd^II. Herein, we report that hydroxylpalladation is not the rate‐determining step and is, in fact, in equilibrium. The newly proposed rate‐determining step involves isomerization and follows the hydroxypalladation step. The mechanism proposed herein is shown to be in excellent agreement with the experimentally observed rate law and rate. Moreover, this mechanism is in consensus with the observed kinetic isotope effects. This report further confirms the outer‐sphere (anti) hydroxypalladation mechanism. Our calculations also ratify that the final product formation proceeds through a reductive elimination, assisted by solvent molecules, rather than through β‐hydride elimination.     

Theoretical Study on the Mechanism of Ni‐Catalyzed Alkyl–Alkyl Suzuki Cross‐Coupling

Ni‐catalyzed cross‐coupling of unactivated secondary alkyl halides with alkylboranes provides an efficient way to construct alkyl–alkyl bonds. The mechanism of this reaction with the Ni/ L1 ( L1 =trans‐N,N′‐dimethyl‐1,2‐cyclohexanediamine) system was examined for the first time by using theoretical calculations. The feasible mechanism was found to involve a Ni^I–Ni^III catalytic cycle with three main steps: transmetalation of [Ni^I( L1 )X] (X=Cl, Br) with 9‐borabicyclo[3.3.1]nonane (9‐BBN)R₁ to produce [Ni^I( L1 )(R₁)], oxidative addition of R₂X with [Ni^I( L1 )(R₁)] to produce [Ni^III( L1 )(R₁)(R₂)X] through a radical pathway, and C? C reductive elimination to generate the product and [Ni^I( L1 )X]. The transmetalation step is rate‐determining for both primary and secondary alkyl bromides. KOiBu decreases the activation barrier of the transmetalation step by forming a potassium alkyl boronate salt with alkyl borane. Tertiary alkyl halides are not reactive because the activation barrier of reductive elimination is too high (+34.7 kcal mol^?1). On the other hand, the cross‐coupling of alkyl chlorides can be catalyzed by Ni/ L2 ( L2 =trans‐N,N′‐dimethyl‐1,2‐diphenylethane‐1,2‐diamine) because the activation barrier of transmetalation with L2 is lower than that with L1 . Importantly, the Ni⁰–Ni^II catalytic cycle is not favored in the present systems because reductive elimination from both singlet and triplet [Ni^II( L1 )(R₁)(R₂)] is very difficult.     

Enantioselective Cross‐Exchange between C−I and C−C σ Bonds

A palladium‐catalyzed enantioselective intramolecular σ‐bond cross‐exchange between C?I and C?C bonds is realized, providing chiral indanones bearing an alkyl iodide group and an all‐carbon quaternary stereocenter. Pd/TADDOL‐derived phosphoramidite is found to be an efficient catalytic system for both C?C bond cleavage and alkyl iodide reductive elimination. In addition to aryl iodides, aryl bromides can also be used for this transformation in the presence of KI. Density‐functional theory (DFT) calculation studies support the ring‐opening of cyclobutanones occuring through an oxidative addition/reductive elimination process involving Pd^IV species.     

Luminescent Palladium(II) Complexes with π‐Extended Cyclometalated [RC^N^NR′] and Pentafluorophenylacetylide Ligands: Spectroscopic,Photophysical, and Photochemical Properties

A series of cyclometalated Pd^II complexes that contain π‐extended R? C^N^N? R′ (R? C^N^N? R′=3‐(6′‐aryl‐2′‐pyridinyl)isoquinoline) and chloride/pentafluorophenylacetylide ligands have been synthesized and their photophysical and photochemical properties examined. The complexes with the chloride ligand are emissive only in the solid state and in glassy solutions at 77 K, whereas the ones with the pentafluorophenylacetylide ligand show phosphorescence in the solid state (λ_max=584–632 nm) and in solution (λ_max=533–602 nm) at room temperature. Some of the complexes with the pentafluorophenylacetylide ligand show emission with λ_max at 585–602 nm upon an increase in the complex concentration in solutions. These Pd^II complexes can act as photosensitizers for the light‐induced aerobic oxidation of amines. In the presence of 0.1 mol % Pd^II complex, secondary amines can be oxidized to the corresponding imines with substrate conversions and product yields up to 100 and 99 %, respectively. In the presence of 0.15 mol % Pd^II complex, the oxidative cyanation of tertiary amines could be performed with product yields up to 91 %. The Pd^II complexes have also been used to sensitize photochemical hydrogen production with a three‐component system that comprises the Pd^II complex, [Co(dmgH)₂(py)Cl] (dmgH=dimethylglyoxime; py=pyridine), and triethanolamine, and a maximum turnover of hydrogen production of 175 in 4 h was achieved. The excited‐state electron‐transfer properties of the Pd^II complexes have been examined.