Simple, Efficient Protocols for the Pd-Catalyzed Cross-Coupling Reaction of Aryl Chlorides and Dimethylamine

Simple and efficient procedures for the Pd-catalyzed cross-coupling reaction of aryl chlorides and dimethylamine are described. At room temperature with a strong base, t-BuXPhos is employed as the supporting ligand; at 110 °C with a weak base, XPhos is employed as the supporting ligand. In each of these cases, commercially available solutions constitute the source of the dimethylamine, and recently disclosed precatalysts constitute the source of the ligand and Pd. This work further expands the utility of these precatalysts in reactions that benefit from an easily activated source of L(1)Pd(0).     

Palladium nanoparticles as efficient green homogeneous and heterogeneous carbon-carbon coupling precatalysts: a unifying view

Pd catalysis of C-C bond formations is briefly reviewed from the angle of nanoparticles (NPs) whether they are homogeneous or heterogeneous precatalysts and whether they are intentionally preformed or generated from a Pd derivative such as Pd(OAc)2. The most studied reaction is the Heck coupling of halogenoarenes with olefins that usually proceeds at high temperature (120-160 degrees C). Under such conditions, the PdII precursor is reduced to Pd0, forming PdNPs from which Pd atom leaching, subsequent to oxidative addition of the aryl halide onto the PdNP surface, is the source of very active molecular catalysts. Other C-C coupling reactions (Suzuki, Sonogashira, Stille, Negishi, Hiyama, Corriu-Kumada, Ullmann, and Tsuji-Trost) can also be catalyzed by species produced from preformed PdNPs. For catalysis of these reactions, leaching of active Pd atoms from the PdNPs may also provide a viable molecular mechanistic scheme. Thus, the term "PdNP catalysis of C-C coupling" used in this review refers to this function of PdNPs as precursors of catalytically active Pd species (i.e., the PdNPs are precatalysts of C-C coupling reactions).     

Reevaluation of the mechanism of the amination of aryl halides catalyzed by BINAP-ligated palladium complexes

Two previous mechanistic studies of the amination of aryl halides catalyzed by palladium complexes of 1,1'-binaphthalene-2,2'-diylbis(diphenylphosphine) (BINAP) are reexamined by the authors of both studies. This current work includes a detailed study of the identity of the BINAP-ligated palladium complexes present in reactions of amines with aryl halides and rate measurements of these catalytic reactions initiated with pure precatalysts and precatalysts generated in situ from [Pd2(dba)3] and BINAP. This work reveals errors in both previous studies, and we describe our current state of understanding of the mechanism of this synthetically important transformation. 31P NMR spectroscopy shows that several palladium(0) species are present in the catalytic system when the catalyst is generated in situ from [Pd2(dba)3] and BINAP, and that at least two of these complexes generate catalytic intermediates. Further, these spectroscopic studies and accompanying kinetic data demonstrate that an apparent positive order in the concentration of amine during reactions of secondary amines is best attributed to catalyst decomposition. Kinetic studies with isolated precatalysts show that the rates of the catalytic reactions are independent of the identity and the concentration of amine, and studies with catalysts generated in situ show that the rates of these reactions are independent of the concentration of amine. Further, reactions catalyzed by [Pd(BINAP)2] with added BINAP are found to be first-order in bromoarene and inverse first-order in ligand, in contrast to previous work indicating zero-order kinetics in both. These data, as well as a correlation between the decay of bromobenzene in the catalytic reaction and the predicted decay of bromobenzene from rate constants of studies on stoichiometric oxidative addition, are consistent with a catalytic process in which oxidative addition of the bromoarene occurs to [Pd(BINAP)] prior to coordination of amine and in which [Pd(BINAP)2], which generates [Pd(BINAP)] by dissociation of BINAP, lies off the cycle. By this mechanism, the amine and base react with [Pd(BINAP)(Ar)(Br)] to form an arylpalladium amido complex, and reductive elimination from this amido complex forms the arylamine.     

Mizoroki-Heck coupling using immobilized molecular precatalysts: leaching active species from Pd pincers, entrapped Pd salts, and Pd NHC complexes

The Mizoroki-Heck reaction is a palladium-catalyzed reaction of both practical importance and scientific significance. Two challenges currently faced by practitioners of the Heck and other palladium-catalyzed coupling reactions are (i) minimizing the costs associated with this reaction by developing high TON catalysts or facilitating catalyst recovery and (ii) elucidating the nature of the active species when using various different precatalysts. These two challenges, one practical and one fundamental, served as our motivation in our studies of immobilized molecular palladium(II) complexes as precatalysts in Mizoroki-Heck reactions. This Forum Article describes our investigations in this area, highlighting our approach to the elucidation of the active catalyst by combining kinetic and poisoning studies of several different related precatalysts, our development of new, selective catalyst poisons, and our quest for stable, recyclable supported Heck, Suzuki, and Sonogashira coupling catalysts. Under high-temperature conditions (120 degrees C), all precatalysts studied are conclusively shown to decompose, liberating soluble, active palladium(0) species that are the true catalysts. Techniques for the elucidation of the nature of the truly active Pd species are enumerated.     

Crystalline Hybrid Solid Materials of Palladium and Decamethylcucurbit[5]uril as Recoverable Precatalysts for Heck Cross‐Coupling Reactions

A series of M? Pd? Me₁₀CB[5] (M=Li, Na, K, Rb, and Cs; Me₁₀CB[5]=decamethylcucurbit[5]uril) hybrid solid materials have been successfully synthesized for the first time through a simple diffusion method. These as‐prepared hybrid solids have been applied as phosphine‐free precatalysts for Heck cross‐coupling reactions with excellent catalytic performance and good recyclability. In the processes of the catalytic reactions, the activated Pd^II species were released from the crystalline hybrid precatalysts and transformed into catalytically active Pd nanoparticles, which have been demonstrated as key to carry on the catalytic reactions for the recoverable precatalysts M? Pd? Me₁₀CB[5] (M=K, Rb, and Cs). It has also been rationalized that the introduction of different alkali metals afforded crystalline hybrid precatalysts with different crystal structures, which are responsible for their diversified stability and reusability presented in Heck reactions.     

Pd-catalyzed regioselective hydroarylation of α-(2-aminoaryl)-α,β-ynones with organoboron derivatives as a tool for the synthesis of quinolines: experimental evidence and quantum-chemical calculations

The Pd-catalyzed hydroarylation of β-(2-aminoaryl)-α,β-ynones with organoboron derivatives, leading to 2,4-diarylquinolines in good to excellent yields through sequential cycloamination, has been investigated. The reaction is catalyzed by both Pd(II) and Pd(0) precatalysts, and can be carried out even under neutral conditions. The regiochemical outcome is inverted with respect to the Pd-catalyzed hydroarylation of β-(2-aminoaryl)-α,β-ynones with aryl iodides. This aspect has been rationalized using quantum-chemical calculations, which show significant differences between the energy barriers of the regioisomeric transition states for the migratory insertion (hydropalladation) step, and are consistent with the charge density of the π complex that undergoes such insertion.     

Pyrazolin-4-ylidenes: a new class of intriguing ligands

The immense success of N-heterocyclic carbenes in recent years has initiated the search for even stronger ligands leading to the discovery of abnormal and remote NHCs. This article reflects our particular interest in the coordination chemistry of pyrazolin-4-ylidenes as a contribution to this field. A modular approach to 4-iodopyrazolium salts with different substitution patterns is described, which upon oxidative addition to Pd(0) gave rise to a library of new Pd(ii) pyrazolin-4-ylidene complexes. A preliminary study showed that selected complexes are active precatalysts in Suzuki-Miyaura and Mizoroki-Heck coupling reactions. The 3,5-substituents of pyrazolin-4-ylidenes are found to have significant effects on complexation and catalytic activities. Finally, the nature of this new class of ligands is discussed, and a future direction for further explorations in this exciting field is envisioned.     

Comparison of dppf‐Supported Nickel Precatalysts for the Suzuki–Miyaura Reaction: The Observation and Activity of Nickel(I)

Ni‐based precatalysts for the Suzuki–Miyaura reaction have potential chemical and economic advantages compared to commonly used Pd systems. Here, we compare Ni precatalysts for the Suzuki–Miyaura reaction supported by the dppf ligand in 3 oxidation states, 0, I and II. Surprisingly, at 80 °C they give similar catalytic activity, with all systems generating significant amounts of Ni^I during the reaction. At room temperature a readily accessible bench‐stable Ni^II precatalyst is highly active and can couple synthetically important heterocyclic substrates. Our work conclusively establishes that Ni^I species are relevant in reactions typically proposed to involve exclusively Ni⁰ and Ni^II complexes.     

Application of Walphos Ligand in the Pd(0)-Catalyzed Asymmetric Allylic Alkylation Reaction

One relatively unexploited commercial ligand, Walphos 1, was tested in the Pd(0)-catalyzed asymmetric allylic alkylation using rac-1,3-diphenyl propenyl acetate and rac-1-acetoxycyclohexene as substrates, methyl malonate as nucleophile, and a variety of Pd precatalysts under standard conditions. The conversions and enantioselectivities were generally good, with the greatest substrate conversion of 99% and a greatest ee of 70%. With the latter cyclic substrate, an enantioselectivity of 98% was obtained, but the conversions were all poor (15–33%).     

Detailed Optimization of Polycondensation Reaction via Direct C–H Arylation of Ethylenedioxythiophene

The polycondensation reaction of 3,4‐ethylenedioxythiophene with 2,7‐dibromo‐9,9‐dioctylfluorene via Pd‐catalyzed direct arylation gives poly[(3,4‐ethylenedioxythiophene‐2,5‐diyl)‐(9,9‐dioctylfluorene‐2,7‐diyl)]. The reaction conditions are optimized in terms of the Pd precatalysts, reaction time, and carboxylic acid additives. The combination of 1 mol% Pd(OAc)₂ and 1‐adamantanecarboxylic acid as an additive is the optimized catalytic system, and it yields the corresponding polymer with a molecular weight of 39 400 in 89% yield. The polycondensation reaction, followed by an end‐capping reaction, effectively provides a linear polymer without Br terminals.     

Palladium nanoparticles stabilized by an ionic polymer and ionic liquid: a versatile system for C-C cross-coupling reactions

Highly stable palladium nanoparticles (Pd NPs), protected by an imidazolium-based ionic polymer (IP) in a functionalized ionic liquid (IL), have been prepared and characterized by transmission electron microscopy (TEM). These Pd NPs are excellent precatalysts for Suzuki, Heck, and Stille coupling reactions and can be stored without undergoing degradation for at least 2 years. The NP-IP-IL system may therefore be considered as an alternative to the traditional palladium on carbon (Pd/C) precatalyst employed in many C-C coupling reactions, also allowing reactions to be conducted under "solvent-free" conditions.     

Third Generation Buchwald Precatalysts with XPhos and RuPhos: Multigram Scale Synthesis,Solvent-Dependent Isomerization of XPhos Pd G3 and Quality Control by 1H- and 31P-NMR Spectroscopy

The third generation Buchwald precatalysts Pd(ABP)(Phos)(OMs) (also known as Phos Pd G3)) with XPhos and RuPhos were prepared in multigram scale by a modified procedure (ABP = fragment of C-deprotonated 2-aminobiphenyl, XPhos = 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl, RuPhos = 2-dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl, OMs⁻ = CH₃SO₃⁻). The ¹H- and ³¹P-NMR spectra of the title complexes and some impurities, measured by various 1D and 2D techniques, were analyzed in detail. The solvent-dependent isomerization of Pd(ABP)(XPhos)(OMs) was studied by NMR, and the X-ray structures of two isomers were determined. The impurities in precatalysts, such as Pd(ABP)(HABP)(OMs) (HABP—neutral 2-aminobiphenyl coordinated to Pd²⁺ in N-monodentate mode) and PdCl₂(XPhos)₂, were identified and characterized by single crystal X-ray diffraction. A simple method for the quick quality control (QC) of the precatalysts, suitable for routine use, was proposed. The method was based on the assessment of the impurity content on the basis of the ¹H-NMR spectra analysis.     

Copper-free and amine-free Sonogashira coupling in air in a mixed aqueous medium by palladium complexes of N/O-functionalized N-heterocyclic carbenes

Highly convenient copper-free and amine-free Sonogashira coupling of aryl bromides and iodides with terminal acetylenes under amenable conditions in air and in a mixed aqueous medium are reported using several new, user friendly and robust palladium precatalysts (1–5) of N/O-functionalized N-heterocyclic carbenes (NHCs). In particular, the precatalysts, 1 and 2, were synthesized from the imidazolium chloride salts by the treatment with PdCl₂ in pyridine in presence of K₂CO₃ as a base while the precatalysts, 3–5, were synthesized from the respective silver complexes by the treatment with (COD)PdCl₂. The DFT studies carried out on the 1–5 complexes suggest the presence of strong NHC–Pd σ-interactions arising out of deeply buried NHC–Pd σ-bonding molecular orbitals (MOs) that account for the inert nature of the metal–carbene bonds and also provide insights into the exceptional stability of these precatalysts.     

Providing support in favor of the existence of a Pd(II)/Pd(IV) 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-C(6)H(4)CO(2)-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)]ClO(4), (X = MeC(O) or ClO(3), L' = another monoanionic pincer ligand derived from 2,6-diacetylpyridine), are precatalysts for the arylation of CH(2)=CHR (R = CO(2)Me, CO(2)Et, Ph) using IC(6)H(4)CO(2)H-2 and AgClO(4). 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.     

An Efficient Low‐Temperature Stille–Migita Cross‐Coupling Reaction for Heteroaromatic Compounds by Pd–PEPPSI–IPent

The reactivity of Pd–PEPPSI (Pyridine, Enhanced, Precatalyst, Preparation, Stabilization, and Initiation) precatalysts in the Stille–Migita cross‐coupling reaction between heteroaryl stannanes and aryl or heteroaryl halides was evaluated. In general, Pd–PEPPSI–IPent (IPent=diisopentylphenylimidazolium derivative) demonstrated high efficiency over a variety of challenging aryl or heteroaryl halides with thiophene‐, furan‐, pyrrole‐, and thiazole‐based organostannanes when compared with Pd–PEPPSI–IPr (IPr=diisopropylphenylimidazolium derivative). The transformations proceeded at appreciably lower temperatures (30–80 °C) than triarylphosphine‐based Pd catalysts, improving the scope of this useful carbon–carbon bond‐forming process.     

Charge-tagged acetate ligands as mass spectrometry probes for metal complexes investigations: applications in Suzuki and Heck phosphine-free reactions

An acetate anion bearing an imidazolium cation as its charge tag was reacted with M(OAc)(2) complexes (where M = Ni, Cu, and Pd; in situ reaction) to form members of a new class of charge-tagged metal complexes. The formation of these unprecedented precatalysts with potential for cross-coupling reactions was confirmed by electrospray ionization (and tandem) mass spectrometry. The catalytic performance of the palladium complex was tested in Heck and Suzuki cross-coupling reactions, often with superior activity and yields as compared with Pd(OAc)(2).     

Mono- and dinuclear bioxazoline-palladium complexes for the stereocontrolled synthesis of CO/styrene polyketones

The coordination chemistry of the chiral bioxazoline ligand (4S,4'S)-2,2'-bis(4-isopropyl-4,5-dihydrooxazole) to Pd(II) provides evidence that the ligand bonding can occur either through chelation of one Pd(II) ion leading to a mononuclear species with the expected cis geometry, or by double bridging of two Pd(II) ions giving a dinuclear complex with trans geometry. The species in solution are identified by 1H NMR spectroscopy. Both the mononuclear and the dinuclear complexes promote the CO/styrene copolymerization, yielding the corresponding polyketone with a fully or a predominantly isotactic microstructure, depending on the reaction medium. The nature of the anion present in the palladium precatalysts affects the polyketone stereochemistry. MALDI-TOF analysis of the copolymers synthesized reveals the presence of p-hydroxyphenolic end-groups, thus confirming and explaining the role of 1,4-hydroquinone as a molecular weight regulator.     

Palladium‐Catalyzed Cross‐Coupling of Alkenyl Carboxylates

Carboxylate esters have many desirable features as electrophiles for catalytic cross‐coupling: they are easy to access, robust during multistep synthesis, and mass‐efficient in coupling reactions. Alkenyl carboxylates, a class of readily prepared non‐aromatic electrophiles, remain difficult to functionalize through cross‐coupling. We demonstrate that Pd catalysis is effective for coupling electron‐deficient alkenyl carboxylates with arylboronic acids in the absence of base or oxidants. Furthermore, these reactions can proceed by two distinct mechanisms for C?O bond activation. A Pd^0/II catalytic cycle is viable when using a Pd⁰ precatalyst, with turnover‐limiting C?O oxidative addition; however, an alternative pathway that involves alkene carbopalladation and β‐carboxyl elimination is proposed for Pd^II precatalysts. This work provides a clear path toward engaging myriad oxygen‐based electrophiles in Pd‐catalyzed cross‐coupling.     

Pentafluorophenyl imidato palladium(II) complexes: catalysts for Suzuki cross-coupling reactions

Novel N-bonded imidato complexes of general formula [Pd(N-N)(C6F5)(imidate)](imidate = maleimidate, succinimidate or phthalimidate; N-N = 2,2'-bipyridine (bipy), 4,4'-dimethyl-2,2'-bipyridine (Me2bipy) or N,N,N',N'-tetramethylethylenediamine (tmeda)), [NBu4][Pd(C6F5)(H2O)(succinimidate)2] and [NBu4][Pd(C6F5)(L)(succinimidate)2](L = PPh3 or t-BuNC) have been synthesised. These complexes are air-, light- and moisture-stable. The crystal structures of [Pd(tmeda)(C6F5)(maleimidate)].H2O.0.5CHCl3, [NBu4][Pd(C6F5)(H2O)(succinimidate)2].H2O and [NBu4][Pd(C6F5)(t-BuNC)(succinimidate)2].2H2O have been determined by X-ray diffraction. Many of these new complexes are shown to be active phosphine-free palladium catalysts/precatalysts for the Suzuki cross-coupling reactions of aryl bromides and aryl chlorides with phenylboronic acid.     

An Examination of the Palladium/Mor‐DalPhos Catalyst System in the Context of Selective Ammonia Monoarylation at Room Temperature

An examination of the [{Pd(cinnamyl)Cl}₂]/Mor‐DalPhos (Mor‐DalPhos=di(1‐adamantyl)‐2‐morpholinophenylphosphine) catalyst system in Buchwald–Hartwig aminations employing ammonia was conducted to better understand the catalyst formation process and to guide the development of precatalysts for otherwise challenging room‐temperature ammonia monoarylations. The combination of [{Pd(cinnamyl)Cl}₂] and Mor‐DalPhos afforded [(κ²‐P,N‐Mor‐DalPhos)Pd(η¹‐cinnamyl)Cl] ( 2 ), which, in the presence of a base and chlorobenzene, generated [(κ²‐P,N‐Mor‐DalPhos)Pd(Ph)Cl] ( 1 a ). Halide abstraction from 1 a afforded [(κ³‐P,N,O‐Mor‐DalPhos)Pd(Ph)]OTf ( 5 ), bringing to light a potential stabilizing interaction that is offered by Mor‐DalPhos. An examination of [(κ²‐P,N‐Mor‐DalPhos)Pd(aryl)Cl] ( 1 b – f ) and related precatalysts for the coupling of ammonia and chlorobenzene at room temperature established the suitability of 1 a in such challenging applications. The scope of reactivity for the use of 1 a (5 mol %) encompassed a range of (hetero)aryl (pseudo)halides (X=Cl, Br, I, OTs) with diverse substituents (alkyl, aryl, ether, thioether, ketone, amine, fluoro, trifluoromethyl, and nitrile), including chemoselective arylations.