Oxidative Addition of Allylic Compounds

Andersson and Backvall observed that the regiochemistry of the palladium-catalyzed reactions of malonate esters with pentadienyl acetates depends on the 

The overall process increases molecular complexity and diversity starting from readily available allylmalonate derivatives. 

Although catalytic deallylation of a-allyl-P-dicarbonyl compounds has not been well applied to organic synthesis, further investigations on the possibility of employing the allylic group as a protective group for acidic C-H bonds are awaited. 

In the light of the rich chemistry of allylic groups and the short history of catalytic carbon-carbon bond cleavage, catalytic removal of allyhc groups is still in its infancy and will find wider apphcation in organic synthesis in the future. 

---

Formation of a Tr-allylpalladium complex 29 takes place by the oxidative addition of allylic compounds, typically allylic esters, to Pd(0). The rr-allylpal-ladium complex is a resonance form of ir-allylpalladium and a coordinated tt-bond. TT-Allylpalladium complex formation involves inversion of stereochemistry, and the attack of the soft carbon nucleophile on the 7r-allylpalladium complex is also inversion, resulting in overall retention of the stereochemistry. On the other hand, the attack of hard carbon nucleophiles is retention, and hence Overall inversion takes place by the reaction of the hard carbon nucleophiles. 

Both stoichiometric and catalytic reactions of allylic compounds via 7r-allyl complexes are known. Reactions of nucleophilic 71-allyl complexes with electrophiles involve oxidation of metals and hence constitutes stoichiometric reactions. 7i-Allyl complexes of Ni, Fe, Mo, Co and others are nucleophilic and undergo the stoichiometric reaction with electrophiles. However, electrophilic 71-allyl complexes react with nucleophiles, accompanying reduction of metals. For example, 71-allylnickel chloride (2) reacts with electrophiles such as aldehydes, generating Ni(II), and hence the reaction is stoichiometric. In contrast, electrophilic 7i-allylpalladium chloride (3) reacts with nucleophiles such as malonate and Pd(0) is generated. Thus repeated oxidative addition of allylic compounds to Pd(0) constitutes a catalytic reaction. 

The direct nucleophilic attack of anilines occurs at both termini of the allylic system of the cationic 73-allylpalladium(II) complex 16 generated by oxidative addition of allylic compounds to a Pd(0) complex. 

Since 7r-allylpaIIadium complexes are formed by oxidative addition of allylic compounds to zerovalent palladium species, and the eliminated HPdX from tt-allylpalladium complexes readily decomposes to regenerate a Pd(0) species with liberation of HX, the elimination processes to 1,3-dienes is catalyzed by palladium complexes. It is considered that the elimination step from HPdX to Pd(0) and HX is reversible therefore, normally the elimination is carried out in the presence of suitable base (B) to capture HX. The catalytic elimination of HX from allylic compounds for the synthesis of 1,3-dienes under mild conditions provides a useful method (Scheme 2). 

Oxidative addition of allylic compounds to Ni(0) precursors is a reliable route to Ni-allyl complexes, with allyl halides being the most commonly used substrates for this purpose. For example, addition of BrGH2G(R)=GH2 (R = Me or H) to Ni(cod)2, followed by reaction with NaBPh4 and dippe, has given the cationic species [Ni(77 -GH2G(R)=GH2)(dippe)]BPh4. Other substrates such as allylic nitriles can also be versatile precursors for the formation of interesting allyl species. Thus, the reaction of Ni(cod)2 with 2-methyl-3-butenenitrile has been reported to proceed by the oxidative activation of the allyl-GN bond to form an allyl intermediate, which has been trapped as the cyano complex 69 in the presence of l,4-bis(diphenylphosphino)butane (dppb), as shown in Scheme 20. The closely related complex of dippe, 71, has been prepared by the reaction of the cationic species 70 " with various sources of cyanide ion. ... 

Similar to the formation of allylmagnesium chloride (25), the oxidative addition of allyl halides to transition metal complexes generates allylmetal complexes 26. However, in the latter case, a 7i-bond is formed by the donation of 7i-electrons of the double bond, and resonance of the n-allvl and 7i-allyl bonds in 26 generates the 7i-allyl complex 27 or (/ -allyl complex. The carbon-carbon bond in the 7i-allyl complexes has the same distance as that in benzene. Allyl Grignard reagent 25 is prepared by the reaction of allyl halide with Mg metal. However, the 7i-allyl complexes of transition metals are prepared by the oxidative addition of not only allylic halides, but also esters of allylic alcohols (carboxylates, carbonates, phosphates), allyl aryl ethers and allyl nitro compounds. Typically, the 7i-allylpalladium complex 28 is formed by the oxidative addition of allyl acetate to Pd(0) complex. 

With the introduction of the highly reactive allylic carbonates, coupling reactions can be carried out under neutral conditions. This is especially important when dealing with compounds that are sensitive to bases. The oxidative addition of allylic carbonates is followed by decarboxylation as the irreversible step to produce the 71-allylpal-ladium alkoxides. Since the alkoxides produced are rather poor nucleophiles, they do not compete with the carbon nucleophile for the 7i-allylpalladium complex but do deprotonate the active methylene compound. Attack of the Nu on the 7i-allylpalladi-um complex leads to the substitution product. 

The alkoxytitanium propene compound Ti(T] -propene)(OTr)2 (46) [153], which is believed to be generated from Ti(0 Pr)4 and two equivalents of /-PrMgCl, reacts with internal alkynes to give titanium-alkyne compounds Ti(ri-alkyne) (0 Pr)2 (47) in quantitative yield (Scheme 6.9) [154,155]. 46 reacts with carboxylic esters to produce cyclo-propan- 1 -ols in modest yields [ 156,157]. Oxidative addition of allyllic halides or allyllic alcohols to 46 proceeds readily to form allyl titanium compounds 48, whose reaction with aldehyde provides a stereoselective synthesis of homoallylic alcohols [153]. 

Scheme 1.10. Stereochemistry of oxidative addition of aUylic compounds to L M to give allyl complexes and nucleophilic attack on the -aUyl ligand.

This method was utilized in the preparation of bicyclic compounds consisting of five-, six-, and seven-manbered rings. Oxidative addition of allylic acetates to palladium(O) takes place with inversion of configuration and intramolecular alkene insertion into the... 

Reactions that proceed under neutral conditions are highly desirable. An important event in TT-allylpalladium chemistry is the introduction of highly reactive allylic carbonates (Sect. V.2.1.3), Their reactions can be carried out under mild neutral conditions. " Also, reactions of allylic carbamates, " allyl aryl ethers, and vinyl epoxides proceed without addition of bases. As shown by the mechanism in Scheme 6, the oxidative addition of allyl methyl carbonates is followed by decarboxylation as an irreversible process to afford TT-allylpalladium methoxide, and the generated methoxide picks up a proton from pronucleophiles (NuH), such as active methylene compounds. This in situ formation of the alkoxide is the reason why the reaction of aUyl carbonates can be carried out without addition of bases from outside. Alkoxides are rather poor nucleophiles, and alkyl allyl ethers are not formed from them. In addition, formation of TT-allylpalladium complexes from allylic carbonates involving decarboxylation is irreversible. In contrast, the formation of TT-allylpalladium acetate from allyl acetate is reversible. 

The butadiene species Tp Rh(77 -C4H6) (Tp = hydrotris(3,5-dimethylpyrazolyl)borato) evolved in the solid state yielding the allyl compound Tp RhH(jy -77 -C3H4Me), as a mixture of exo- and r/o-isomers. The complex TpMe2Rh(coe)(MeCN) underwent oxidative addition of allyl bromide at room temperature to give Tp Rh(<7-allyl)Br(MeCN). On prolonged reaction time or heating, this complex converted to the 7r-allyl complex Tp Rh(7 -allyl)Br with the liberation of MeCN (Scheme 57). ... 

TT-Aliylpalladium chloride reacts with a soft carbon nucleophile such as mal-onate and acetoacetate in DMSO as a coordinating solvent, and facile carbon-carbon bond formation takes place[l2,265], This reaction constitutes the basis of both stoichiometric and catalytic 7r-allylpalladium chemistry. Depending on the way in which 7r-allylpalladium complexes are prepared, the reaction becomes stoichiometric or catalytic. Preparation of the 7r-allylpalladium complexes 298 by the oxidative addition of Pd(0) to various allylic compounds (esters, carbonates etc.), and their reactions with nucleophiles, are catalytic, because Pd(0) is regenerated after the reaction with the nucleophile, and reacts again with allylic compounds. These catalytic reactions are treated in Chapter 4, Section 2. On the other hand, the preparation of the 7r-allyl complexes 299 from alkenes requires Pd(II) salts. The subsequent reaction with the nucleophile forms Pd(0). The whole process consumes Pd(ll), and ends as a stoichiometric process, because the in situ reoxidation of Pd(0) is hardly attainable. These stoichiometric reactions are treated in this section. 

In addition, a catalytic version of Tt-allylpalladium chemistry has been devel-oped[6,7]. Formation of the Tr-allylpalladium complexes by the oxidative addition of various allylic compounds to Pd(0) and subsequent reaction of the complex with soft carbon nucleophiles are the basis of catalytic allylation. After the reaction, Pd(0) is reformed, and undergoes oxidative addition to the allylic compounds again, making the reaction catalytic.-In addition to the soft carbon nucleophiles, hard carbon nucleophiles of organometallic compounds of main group metals are allylated with 7r-allylpalladium complexes. The reaction proceeds via transmetallation. These catalytic reactions are treated in this chapter. 

Wylation under neutral conditions. Reactions which proceed under neutral conditions are highly desirable, Allylation with allylic acetates and phosphates is carried out under basic conditions. Almost no reaction of these allylic Compounds takes place in the absence of bases. The useful allylation under neutral conditions is possible with some allylic compounds. Among them, allylic carbonates 218 are the most reactive and their reactions proceed under neutral conditions[13,14,134], In the mechanism shown, the oxidative addition of the allyl carbonates 218 is followed by decarboxylation as an irreversible process to afford the 7r-allylpalladium alkoxide 219. and the generated alkoxide is sufficiently basic to pick up a proton from active methylene compounds, yielding 220. This in situ formation of the alkoxide. which is a... 

As far as the reactions with benzyl chlorides are concerned (74), the oxidative addition of benzyl chloride and substituted benzyl chlorides to palladium atoms yields rj -benzylpalladium chloride dimers. The parent compound, bis(l,2,3-7 -benzyl)di-/i,-chloro-palladium(II), quantitatively adds four molecules of PEts by first forcing the rj -benzyl-iy -benzyl transformation, with subsequent breakage of the Pd-Cl bridges to form trans-bistPEtsKbenzyDchloroPddI). The spectral characteristics of the parent molecule are indicative of the allylic type of bonding. Similar i7 -benzyl compounds were formed from 4-methylbenzyl chloride, 2-chloro-l,l,l-trifluoro-2-phenylethane, and 3,4-dimethylbenzyl chloride. 

The development of the Grignard-type addition to carbonyl compounds mediated by transition metals would be of interest as the compatibility with a variety of functionality would be expected under the reaction conditions employed. One example has been reported on the addition of allyl halides to aldehydes in the presence of cobalt or nickel metal however, yields were low (up to 22%). Benzylic nickel halides prepared in situ by the oxidative addition of benzyl halides to metallic nickel were found to add to benzil and give the corresponding 3-hydroxyketones in high yields(46). The reaction appears to be quite general and will tolerate a wide range of functionality. 

Since nucleophilic addition to a metal-coordinated alkene generates a cr-metal species bonded to an -hybridized carbon, facile 3-H elimination may then ensue. An important example of pertinence to this mechanism is the Wacker reaction, in which alkenes are converted into carbonyl compounds by the oxidative addition of water (Equation (108)), typically in the presence of a Pd(n) catalyst and a stoichiometric reoxidant.399 When an alcohol is employed as the nucleophile instead, the reaction produces a vinyl or allylic ether as the product, thus accomplishing an etherification process. 

The reaction proceeds through ligand exchange and a subsequent P-elimination akin to the oxidative addition of Cp2Zr to allylic ethers [58], In this way, allyltitanium compounds can be obtained from readily available allylic alcohol derivatives and inexpensive Ti(OiPr)4. The method allows the preparation of functionalized allyltitaniums bearing functional groups such as ester or halide (Scheme 13.28). 

A one-pot synthesis of 3,3-disubstituted indolines was achieved by taking advantage of a sequential carbopalladation of allene, nucleophile attack, intramolecular insertion of an olefm and termination with NaBPh4 (Scheme 16.6) [10]. First, a Pd(0) species reacts with iodothiophene selectively to afford ArPdl, probably because the oxidative addition step is facilitated by coordination with the adjacent sulfur atom. Second, the ArPdl adds to allene, giving a Jt-allylpalladium complex, which is captured by a 2-iodoaniline derivative to afford an isolable allylic compound. Under more severe conditions, the oxidative addition of iodide to Pd(0) followed by the insertion of an internal olefm takes place to give an alkylpalladium complex, which is transmetallated with NaBPh4 to release the product. 

The reaction starts with an oxidative addition of an allylic compound to palladium(O) and a Tt-allyl-palladium complex forms. Carboxylates, allyl halides, etc. can be used. In practice one often starts with divalent palladium sources, which require in situ reduction. This reduction can take place in several ways, it may involve the alkene, the nucleophile, or the phosphine ligand added. One can start from zerovalent palladium complexes, but very stable palladium(O) complexes may also require an incubation period. Good starting materials are the 7t-allyl-palladium intermediates ... 

The mechanism of the Zn chloride-assisted, palladium-catalyzed reaction of allyl acetate (456) with carbonyl compounds (457) has been proposed [434]. The reaction involves electroreduction of a Pd(II) complex to a Pd(0) complex, oxidative addition of the allyl acetate to the Pd(0) complex, and Zn(II)/Pd(II) transmetallation leading to an allylzinc reagent, which would react with (457) to give homoallyl alcohols (458) and (459) (Scheme 157). Substituted -lactones are electrosynthesized by the Reformatsky reaction of ketones and ethyl a-bromobutyrate, using a sacrificial Zn anode in 35 92% yield [542]. The effect of cathode materials involving Zn, C, Pt, Ni, and so on, has been investigated for the electrochemical allylation of acetone [543]. 

Allyltin difluoroiodide, formed in situ by the oxidative addition of stannous fluoride to allyl iodide, is found to react with carbonyl compounds to give the corresponding homoallylic alcohols in excellent yields under mild reaction conditions (9). 

---