Reactions with Arylpalladium Compounds

Palladation of aromatic compounds with Pd(OAc)2 gives the arylpalladium acetate 25 as an unstable intermediate (see Chapter 3, Section 5). A similar complex 26 is formed by the transmetallation of PdX2 with arylmetal compounds of main group metals such as Hg Those intermediates which have the Pd—C cr-bonds react with nucleophiles or undergo alkene insertion to give oxidized products and Pd(0) as shown below. Hence, these reactions proceed by consuming stoichiometric amounts of Pd(II) compounds, which are reduced to the Pd(0) state. Sometimes, but not always, the reduced Pd(0) is reoxidized in situ to the Pd(II) state. In such a case, the whole oxidation process becomes a catalytic cycle with regard to the Pd(II) compounds. This catalytic reaction is different mechanistically, however, from the Pd(0)-catalyzed reactions described in the next section. These stoichiometric and catalytic reactions are treated in Chapter 3. 

With regard to the mechanism of these Pd°-catalyzed reactions, little is known in addition to what is shown in Scheme 10-62. In our opinion, the much higher yields with diazonium tetrafluoroborates compared with the chlorides and bromides, and the low yields and diazo tar formation in the one-pot method using arylamines and tert-butyl nitrites (Kikukawa et al., 1981 a) indicate a heterolytic mechanism for reactions under optimal conditions. The arylpalladium compound is probably a tetra-fluoroborate salt of the cation Ar-Pd+, which dissociates into Ar+ +Pd° before or after addition to the alkene. An aryldiazenido complex of Pd(PPh3)3 (10.25) was obtained together with its dediazoniation product, the corresponding arylpalladium complex 10.26, in the reaction of Scheme 10-64 by Yamashita et al. (1980). Aryldiazenido complexes with compounds of transition metals other than Pd are discussed in the context of metal complexes with diazo compounds (Zollinger, 1995, Sec. 10.1). 

Arylation of alkenes catalyzed by palladium compounds is known as the Heck reaction [65]. While these reactions are very sensitive to steric effects, subtle electronic contributions to the regiochemical outcome may be assessed by comparing reactions of alkenes with similar substitution patterns. The arylating agents, being the nucleophilic arylpalladium species, tend to dictate the facility of their reaction with unsym-metrical, electron-deficient alkenes. 

The preparation of organopalladium compounds by exchange reactions of palladium salts and organo-lead, -tin, or -mercury compounds is apparently not the only way that they can be obtained but it does seem to be the most useful way. Convincing evidence is now available to show that direct metalation of aromatic compounds with palladium salts (palladation) can occur. Since the initial report of Cope and Siekman 32> that palladium chloride reacted readily with azobenzene to form an isolable chelated, sigma-bonded arylpalladium compound, several additional chelated arylpalladium compounds have been prepared. 

These reactions are considered to involve insertion of the unsaturated compounds to arylpalladium species followed by the formation of palladacycle intermediates. Oxidative addition of another halide molecule to them leads to the products. In the reaction with norbornene [105 -108] and diphenylacety-lene [109],the corresponding 3 1 and4 1 products and 3 1 product,respectively, are also formed under somewhat different conditions. The mechanisms to account for the formation of these unusual products involving multiple C-H cleavage steps have been proposed. It is noted that, in contrast to Eq. (49), treatment of aryl bromides with aliphatic internal alkynes gives allene derivatives (Eq.50) [110]. 

The Stille coupling involves heating a halide, a stannane and a catalyst in a suitable solvent, such as toluene or DMF. No base is required. The conditions are relatively straightforward, with little overall variation, apart from the catalyst. However, if a triflate is used instead of a halide, the reaction may not succeed, as transmetallation of aryltin compounds with arylpalladium triflates is often difficult. Addition of a halide source, such as lithium chloride, usually solves this problem as it allows the formation of the arylpalladium chloride, which can undergo transmetallation. 

While the scope is somewhat limited and the yields are only moderate, this process provides a very direct and convenient route to 2,3-disubstituted indenones that would be quite hard to prepare by most other procedures. Mechanistically, it is not clear if this reaction proceeds by addition of the vinylic palladium intermediate across the aldehyde moiety and subsequent p-hydride elimination, or whether the aldehyde C-H bond undergoes oxidative addition to the vinylic palladium intermediate and two subsequent reductive eliminations generate the final indenone product. Related stoichiometric arylpalladium compounds have been reported to react with alkynes to afford both indenones and indenols [109,130]. 

The mechanism begins with oxidative addition of Pd(II) to the C2-Brl bond to give an arylpalladium(II) compound. (Although the Pd compound that is added to the reaction mixture is Pd(IE), it is reduced in situ... 

Acyl halides are reactive compounds and react with nucleophiles without a catalyst, but they are activated further by forming the acylpalladium intermediates, which undergo insertion and further transformations. The decarbonyla-tive reaction of acyl chlorides as pseudo-halides to form the arylpalladium is treated in Section 1.1.1.1. The reaction without decarbonylation is treated in this section. 

On the basis of the reaction of conjugated dienes with unsaturated halides in the presence of external nucleophiles, an elegant intramolecular version leading to a-alkylidene-y-lactams, has been developed (Scheme 8.19). Starting with an aryl halide, the regioselective insertion of an arylpalladium halide to the triple bond of acyclic compound 42 gives the c-vinylpalladium intermediate 43. Subsequent intramolecular carbopalladation of the diene affords a re-allyl palladium intermediate... 

Over 35 years ago, Richard F. Heck found that olefins can insert into the metal-carbon bond of arylpalladium species generated from organomercury compounds [1], The carbopalladation of olefins, stoichiometric at first, was made catalytic by Tsutomu Mizoroki, who coupled aryl iodides with ethylene under high pressure, in the presence of palladium chloride and sodium carbonate to neutralize the hydroiodic acid formed (Scheme 1) [2], Shortly thereafter, Heck disclosed a more general and practical procedure for this transformation, using palladium acetate as the catalyst and tri-w-butyl amine as the base [3], After investigations on stoichiometric reactions by Fitton et al. [4], it was also Heck who introduced palladium phosphine complexes as catalysts, enabling the decisive extension of the ole-fination reaction to inexpensive aryl bromides [5],... 

Abnormal olefin arylation reactions which are of interest mechanistically and preparatively occur with some allylically substituted compounds. The ailylic esters and ethers appear normal and produce cinnamyl derivatives exclusively while ailylic alcohols and chlorides are abnormal. Ailylic alcohols and "arylpalladium acetates form 3-arylaldehydes from primary ailylic alcohols and 3-arylketones from secondary alcohols 3°). The mechanism of reaction apparently involves anti-Markovnikov addition of the palladium compound to the double bond followed by elimination of the hydrogen atom on the hydroxyl-bearing carbon rather than the benzylic hydrogen. This again would be elimination of the more electronegative hydrogen atom. 

Aromatic compounds react with palladium(II) salts such as PdCOAc) and Na2PdCl4 via an electrophilic aromatic substitution process to give arylpalladium complexes. This type of reaction is most commonly observed with aromatic rings bearing a substituent that makes a fi e- or six-membered chelate ring with palladium in the metallation products (eq (87)) [118]. In this case, the electrophilic substitution occurs only at the ortho position to the chelating substituent. 

Aromatic compounds can react with Pd(II) species, typically Pd(OAc)2, via cleavage of their C-H bonds to give arylpalladium(II) species (Scheme 1, mechanism D). Therefore, the arylation of alkenes can be performed directly using arenes and aromatic heterocycles [10, 11]. In this arylation, halogenation of arenes can be omitted, but an oxidizing reagent for the reoxidation of Pd(0) to Pd(II) should be added to make the reaction catalytic. 

The 1,2-insertion of alkenes into transition metal-carbon o-bond leads to C-C bond formation under mild conditions, as described in Chapter 6. This reaction is considered to be a crucial step in the coordination polymerization and carbometalation of alkenes catalyzed by transition metal complexes. A common and important carbometalation is the Heck-type arylation or vinylation of alkene catalyzed by Pd complexes [118], The arylation of alkene, most typically, involves the formation of arylpalladium species and insertion of alkene into the Pd-aryl bond as shown in Scheme 5.20. The arylpalladium species is formed by the oxidative addition of aryl halides to Pd(0) complexes or the transmetalation of aryl compounds of main group metals with Pd(II) complexes. Insertion of alkene into the Pd-aryl bond produces 2-arylalkylpalladium species whose y6-hydrogen elimination leads to the arylalkene. Oxidative chlorination of the 2-arylalkylpalladium intermediate forms chloroalkanes as the product. 

Contrarily, the nickel-catalysed SM reactions are always carried out in dry solvents. Since the arylnickel complexes have more ionic character than the corresponding arylpalladiums, the former are generally more reactive and sensitive to water (and other protic compounds) and furnish the protonated (reductive dehalogenation) arene from the parent aryl halide. However, the most common base in the nickel-catalysed SM reactions is K3P04 nH20. The fact, that a small amount of dehalogenation products was isolated, supports the arylnickel protonation side-reaction, either with water (from solvent(s) or K3P04 H20) or any other protic source. 

It is a rare honour to be asked to write a preface to a book based on chemistry which you helped begin. My research in palladium chemistry began before 1968. Initial results were obtained by preparing arylpalladium salts by exchange reactions between Pd(OAc>2 or PdCl2 and aryl-mercurials, -lead or -tin compounds and reacting these with alkenes to... 

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