Nucleophilic substitution palladium-catalyzed elimination

Palladium-catalyzed allylic oxidations, in contrast, are synthetically useful reactions. Palladium compounds are known to give rise to carbonyl compounds or products of vinylic oxidation via nucleophilic attack on a palladium alkene complex followed by p-hydride elimination (Scheme 9.16, path a see also Section 9.2.4). Allylic oxidation, however, can be expected if C—H bond cleavage precedes nucleophilic attack 694 A poorly coordinating weak base, for instance, may remove a proton, allowing the formation of a palladium rr-allyl complex intermediate (89, path by694-696 Under such conditions, oxidative allylic substitution can compete... 

A one-pot procedure for the palladium-catalyzed allylation/cyclization of o-alkynyltrifluoroacetanilides 57a [57] and o-alkynylphenols 57b [58] was developed by Cacchi et al. (Scheme 20). This method provides a valuable tool for the synthesis of 2-substituted-3-allylindoles 58a and 2-substituted-3-allylbenzofurans 58b. It was reported that reaction proceeded through the formation of X-allyl derivatives, which form 7r-allylpalladium species 59. A subsequent rearrangement of 59 would then lead to the 7r-allylpalladium species 60. Intramolecular nucleophilic attack of the hetero atom across the activated carbon-carbon triple bond in 60, followed by reductive elimination of Pd(0) gives the products 58. A similar reaction was reported by Balme et al. [59]. 

Palladium salts also promote the addition of nucleophiles to alkenes and alkynes. The Pd-catalyzed additions of nucleophiles to alkynes, which is useful for intramolecular cyclizations such as the isomerization of 2-alkynylphenols to benzofurans, proceeds by exactly the same mechanism as does the Hg-catalyzed reaction. However, the Pd-catalyzed additions of nucleophiles to alkenes takes the course of substitution rather than addition because alkylpalladium complexes are unstable toward /3-hydride elimination. The Pd-catalyzed nucleophilic substitutions of alkenes are discussed later in this chapter (Section 6.3.6). 

Palladium-Catalyzed Reactions. Numerous nucleophiles react with (l-bromovinyl)trimethylsilane in the presence of palladium complexes. The bromine has been substituted by phenylthio, vinyl, and aryl groups. This approach gives reasonable yields of the desired products. However, the substitution reactions sometimes lack regiospecificity. For example, a mixture of regioisomers was obtained in eq 6. Two mechanisms have been proposed for the formation of the -substituted product. One involves an elimination step to give trimethylsilylacetylene as an intermediate, which then undergoes catalyzed additions with the nucleophile at either the a- or positions. The other mechanism involves the formation of a pentacoordinated palladium intermediate, leading to the formation of isomeric products. ... 

The vinylogous elimination to give alkenylcyclopropanes may also be effected via rt-allyl palladium complexes34,35. The palladium(0)-catalyzed substitution of allylic esters with stabilized carbon nucleophiles via 7i-allyl palladium derivatives stereospecifically proceeds with net retention (double inversion) of configuration. Thus, the chirality of an allylic substrate is transferred to resultant alkenylcyclopropanes in the intramolecular S J/ reaction via 7i-allyl palladiums (equation 21)36,3. ... 

A wide variety of nucleophiles add to an -rf-allyl ligand. Desirable nucleophiles typically include stabilized carbanions such as CH(COOR)2 or 1° and II0 amines. Unstabilized nucleophiles such as MeMgBr or MeLi often attack the metal first and then combine with the n-allyl by reductive elimination. The Tsuji-Trost reaction, which is typified by the addition of stabilized carbanions to T 3—allyl ligands complexed to palladium followed by loss of the resulting substituted alk-ene, comprises an extremely useful method of constructing new C-C bonds, and many applications of this reaction have appeared in the literature.61 Equation 8.43 illustrates an example of a Pd-catalyzed addition of a stabilized enolate to an allyl acetate.62 The initial step in the catalytic cycle is oxidative addition of the allyl acetate to the Pd(0) complex, followed by nq1 to nq3—allyl isomerization, and then attack by the nucleophile to a terminal position of the T 3—allyl ligand. We will discuss the Tsuji-Trost reaction, especially in regard to its utility in chiral synthesis,63 more extensively in Chapter 12. 

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