Palladium complexes olefin, nucleophilic attack

In most palladium-catalyzed oxidations of unsaturated hydrocarbons the reaction begins with a coordination of the double bond to palladium(II). In such palladium(II) olefin complexes (1), which are square planar d8 complexes, the double bond is activated towards further reactions, in particular towards nucleophilic attack. A fairly strong interaction between a vacant orbital on palladium and the filled --orbital on the alkene, together with only a weak interaction between a filled metal d-orbital and the olefin ji -orbital (back donation), leads to an electrophilic activation of the alkene9. 

Alike olefins, allenes also undergo palladium mediated addition in the presence of N-H or O-H bonds. Although these reactions show some similarity to Wacker-type processes, from the mechanistic point of view they are quite different. Allenes, such as the cr-aminoallene in 3.69., usually undergo addition with palladium complexes (e.g. carbopalladation in 3.69. and 3.70., or hydropalladation in 3.71.), which leads to the formation of a functionalized allylpalladium complex. Subsequent intramolecular nucleophilic attack by the amino group leads to the closure of the pyrroline ring.87... 

Secondary amines can be added to certain nonactivated olefins if palladium(II) complexes are used as catalysts.208 The complexation lowers the electron density of the double bond, facilitating nucleophilic attack.209 Markovnikov orientation is observed and the addition is anti.210... 

Several catalytic systems have been investigated for hydroamination of unsaturated bonds [16]. Takahashi et al. reported the telomerization of 1,3-dienes in the presence of an amine leading to octadienylamine or allylic amines when palladium catalysts are used in association with monodentate or bidentate phosphine ligands, respectively [17]. Dieck et al. demonstrated the beneficial effect of addition of an amine hydroiodic salt in the hydroamination reaction of 1,3-dienes in which the allylic amines are produced via an intermediate Jt-allyl palladium complex [18]. Coulson reported the Pd-catalyzed addition of amines to allenes where dimerization is incorporated [4]. This reaction presumably proceeds via a cyclic palladium intermediate in which the Pd activates the olefinic bond for nucleophilic attack the reactions are therefore different from pronucleophilic additions. 

Palladium complexes are generally superior catalysts for oxidation reactions, whereas other noble metals are more active for other reactions, e.g., rhodium for hydroformylation. All of these reactions seemingly involve activation of the olefin substrate by rr-complex formation with the noble metal catalyst.513 The oxidation reactions discussed in the following generally depend on nucleophilic attack on the coordinated olefins (or other hydrocarbons) to effect oxidation of the substrate. 

The palladium-catalyzed [3 + 2] cycloaddition of vinylic oxirane 20a [42] and aziridine 20b [39] with the activated olefin 4a for the formation of five membered cyclic ether 21a and pyrrolidine derivative 21b has also been reported in our laboratories. The mechanistic issue is very much similar to that discussed in Scheme 9. Pd(0) catalyst added oxidatively to 20 to produce the 7r-allylpalladium complex 22. The Michael addition of a hetero nucleophile in 22 to the activated olefin 4a gives 23 which undergoes intramolecular nucleophilic attack on the inner 7r-allylic carbon atom to give the cy-clized products 21 and Pd(0) species is generated (Scheme 10). Similarly, the palladium-catalyzed [3 + 2] cycloaddition of vinylic oxirane 20a with the N-losylimincs 24 is also known (Scheme 11) [43]. Intermolecular cycloaddition of vinyl epoxides and aziridines with the heterocumulenes such as isocyanates, carbodiimides and isothiocyanates is also known [44,45]. Alper et al. reported the regio- and enatioselective formation of the thiaolidine, oxathiolane, and dithiolane derivatives by the palladium-catalyzed cyclization reaction of 2-vinylthiirane with heterocumulenes [46]. 

Interestingly, this 1,4-carbochlorination occurs syn, which constrasts with that via the vinylpalladation in Eq.(49), which occurs anti. An explanation for this difference is that the allylsilane attacks the palladium-diene complex anti, leading to a rrans-carbopalladation of the double bond. This is the first example of nucleophilic attack by an allylsilane on an olefin coordinated to a metal. Direct evidence for a frans-carbopalladation was provided by the isolation of the proposed 7r-allyl intermediate of Eq.(51) as its chlorodimer 98a from reaction of 97 with Li2PdCl4 in the absence of benzoquinone [Eq.(52)] [119b]. The trans relationship between palladium and the carbon that has attacked the diene was established by the reporter ligand technique used for 41 in Section 8.3.1.1 under Intramolecular 1,4-diacyloxylation . 

Additions to nonactivated olefins and dienes are important reactions in organic synthesis [1]. Although cycloadditions may be used for additions to double bonds, the most common way to achieve such reactions is to activate the olefins with an electrophilic reagent. Electrophilic activation of the olefin or diene followed by a nucleophilic attack at one of the sp carbon atoms leads to a 1,2- or 1,4-addition. More recently, transition metals have been employed for the electrophilic activation of the double bond [2]. In particular, palladium(II) salts are known to activate carbon-carbon double bonds toward nucleophilic attack [3] and this is the basis for the Wacker process for industrial oxidation of ethylene to acetaldehyde [41. In this process, the key step is the nucleophilic attack by water on a (jt-ethylene)palladium complex. 

Doyle has put forward arguments against the intermediacy of such complexes in catalytic cyclopropanation . Firstly, metal coordination activates the alkene to nucleophilic attack. Hence, an electrophilic metal carbene would add only reluctantly or not at all. Secondly, the stable PdCl2 complexes of dienes 8 and 428 do not react with ethyl diazoacetate, even if Rh fOAc) or PdCljfPhCbOj is added. The diazoester is decomposed only when it is added to a mixture of the Pd complex and excess diene. These results exclude the metal-carbene-olefin intermediate, but they leave open the possibility of metal carbene interaction with an uncomplexed olefin molecule. The preferred formation of exo-cyclopropanes in the PdCyPhCN) -catalyzed reactions between 8 and N2CHCOOEt or N2CPh2, with exo. endo ratios virtually identical to those observed upon cyclopropanation of monoolefin 429, also rule out coordination of a palladium carbene to the exocyclic double bond of 8 prior to cyclopropanation of the endocyclic double bond. 

Since palladium(II) is electrophilic, olefins are activated toward nucleophiles by coordination to palladium(II) species. The attack of nucleophiles occurs at the more substituted vinylic carbon from the anti side of palladium to give alkylpalladium complexes (eq (92)) [123]. 

Nucleophilic attack of the arene on the palladium-olefin complex I with loss of HCI... 

Palladium(II) catalysts have been found to be more effective than platinum(II), presumably owing to the lesser stability of the olefin complexes of the former resulting from minimized back-bonding in palladium. By reducing the electron density around the double bond, nucleophilic attack on the double bond is facilitated. 

In contrast to the processes based on the external attack of a nucleophile on the coordinated CO or olefin ligands on Pd(II) species, where re-oxidation of the Pd(0) produced to reactive Pd(II) presents a considerable problem, no such problem is involved in reaction of a Pd(0) complex with allylic substrates. As we have already discussed in Schemes 1.9 and 1.10, allylic compounds such as allylic acetates or carbonates readily oxidatively add to Pd(0) species to form 7 -allyl palladium(II) complexes that are susceptible to nucleophilic attack. The catalytic process converting allylic substrates to produce allylation products of nucleophiles has found extensive uses in organic synthesis, notably in the work of Tsuji and Trost. Employment of a chiral ligand in the catalytic allylation of nucleophiles allows catalytic asymmetric synthesis of allylation... 

The insertion of olefins into the metal-oxygen bonds of isolated alkoxo, phenoxo, or hydroxo compounds has been observed directly in a few cases. As will be noted in Chapter 11, a hydroxy or alkoxyalkyl group can be formed by insertion of an olefin into a metal-oxygen bond or by attack of hydroxide or an alkoxide on a coordinated olefin. Many studies described in Chapter 11 imply that this type of compound is formed by nucleophilic attack on a coordinatively saturated olefin complex, and this reaction has been proposed as the C-0 bond-forming step during oxidations of olefins catalyzed by palladium complexes. However, Henry provided some of the first evidence that the C-0 bond forms by insertion of olefins into metal-hydroxo and -alkoxo complexes under certain reaction conditions. ... 

Kurosawa has shown that the related palladium(II) olefin complex [( ti -C5H5)Pd(Ph3P) (CHj=CHj)] undergoes clean trans attack by both methoxide and the anion of acety-lacetone. These examples of additions to iron- and palladium-olefin complexes occur by attack only at the ligand and lead to stable o-alkyl products because the metal center is coordinatively saturated. This coordinative saturation disfavors attack at the metal that would lead to either products from syn addition or displacement of the olefin. The cr-alkyl complexes that are products of these examples of nucleophilic attack are stable because the most common mode for decomposition of o-alkyl complexes, 3-hydrogen elimination, requires the presence of a vacant coordination site cis to the alkyl group, as noted in Chapters 8 and 9. Such a site is not present in these cr-alkyl products. 

In contrast to complexes of palladium(II) complexes ligated by chelating olefins, palladium(II) complexes ligated by simple monoolefins generate products that are less stable toward p-hydrogen elimination and more often react with nucleophiles to simply displace the olefin from the metal center. Yet, examples of nucleophilic attack on ethylene... 

Many reactions of amines with palladium- and platinum-olefin complexes have been reported. Akermark showed that nucleophiles add to palladium-olefin complexes to generate aminoalkyl complexes, as shown by the example in Equation 11.26. In this case, reactions of a bis-olefin dichloropalladium complex with amines occurs by splitting of the chloro-bridged dimer by the first equivalent of amine to give a neutral olefin-ligated palladium-amine complex that undergoes attack of the coordinated alkene by a second equivalent of amine. The stereochemistry of the amination is cleanly trans. Akermark and Zetterberg isolated and characterized by C NMR spectroscopy the a-alkyl complexes formed by the amination of both cis- and frans-2-butene, and the stereochemistry of the product alkyl complexes results from external attack by amines, as shown in Scheme 11.5. 

Hegedus developed an olefin amination process that generates indoles by intramolecular nucleophilic attack of substituted amines on allylarenes (Equation 11.27). In this process, an N-tosyl arylamine attacks the coordinated olefin of an allyl group in the ortho position of the aniline, and p-hydrogen elimination generates a tautomer of indole and a reduced palladium complex. This reduced complex is then re-oxidized by quinone to regenerate the starting palladium(II), and the product tautomerizes to the final indole product. This cycle was one of the earliest catalytic olefin aminations. 

Oxygen nucleophiles, such as water, alcohols, and carboxylic acids, also attack coordinated olefins in simple (monoolefin)palladium(II) complexes. These nucleophiles do not displace the olefin from the metal because they are poor ligands for the soft palladium(II). 

Nucleophilic attack of stabilized carbon nucleophiles on coordinated olefins is also known. Hegedus developed the alkylation of olefins shown in Equation 11.31. The (olefin)palladium(II) chloride complexes did not react with malonate nucleophiles, but the triethylamine adduct does react with this carbon nucleophile to provide the alkylation product. This reaction has recently been incorporated into a catalytic alkylation of olefins by Widenhoefer. - Intramolecular reaction of the 1,3-dicarbonyl compounds with pendant olefins in the presence of (GHjCNl PdCl occurs to generate cyclic products containing a new C-C bond (Equation 11.32). Some intermolecular reactions with ethylene and propylene have also been developed by this group. Deuterium labeling studies (Equation 11.32) have shown that the addition occurs by external attack on the coordinated olefin. ... 

Hydroaminations occurring by nucleophilic attack on ir-ligands are the oldest class of hydroamination and are discussed first. A mechanism for the hydroamination of alk-enes and alkynes catalyzed by palladium(II) complexes is shown in Scheme 16.16. By this pathway, coordination of the alkene or alkyne through the -ir-system occurs to generate a cationic or electron-poor, neutral metal-olefin or metal-alkyne complex. Nucleophilic attack of the amine on the coordinated olefin or alkyne then occurs. Nucleophilic attack on coordinated olefins and alkynes is presented in detail in Chapter 11. As noted in Chapter 11, this nucleophilic attack occurs at the internal position of an alkene or alkyne. 

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