Allyl palladium, reaction with

The mechanism of this reaction was considered on the basis of hydropalladation (Scheme 14). To minimize steric repulsions, the palladium hydride complex approaches the C=CH2 moiety of the allene in the anti-Markovnikov mode from the opposite side of the substituent. This addition gives a 7t—allyl palladium complex with the (Z)-configuration,18 which is converted to the (Z)-product by C-P bond formation, with regeneration of the Pd(0) catalyst. 

The reaction of tt -allyl palladium complexes with hydrogen causes decomposition of the compounds, and produces either alkenes or alkanes, depending on the degree of substitution of the TT-aUyl complex and the reaction conditions. Hydride reagents, such as NaBUi and LiAUTi, also reduce the aUylic group to alkanes or alkenes. 

Wacker-type oxidative reactions of olefins with nucleophiles, reactions of zr-allyl-palladium complexes with nucleophiles, reactions based on chelation, and trans-metallation of organomercury compounds. 

In contrast to soft nucleophiles which attack the allyl face opposite the palladium complex, hard nucleophiles (e.g., organozinc reagents) first coordinate to the metal center and then are transferred intramolecularly to the allyl ligand (see, e.g.. Table 1 in [13]). Therefore, the reaction of allyl-palladium complexes with hard nucleophiles usually involves retention of configuration. However, the classification as soft and hard nucleophiles is not always unambiguous. With acetate as the nucleophile, e.g., the stereoselectivity depends on the reaction conditions and both overall inversion as well as retention have been observed [18]. 

Activated methylene compounds such as dimethyl malonate have found substantial utility in palladium catalyzed allylic substitution reactions. Accordingly, the Krapcho decarboxylation is often used in conjunction with these reactions. As an example, the first total synthesis of enantiomerically pure (-)-wine lactone has utilized the sequence of reactions.27 First, the allylic substitution reaction of 2-cyclohexen-l-yl acetate (49) with alkali sodium dimethylmalonate yielded 51 with high enantioselectivity, as a result of the use of chiral phosphine ligand 50. The malonate was then subjected to Krapcho decarbomethoxylation using NaCl, H2O, and DMSO at 160 °C to yield 52. This reaction has been used similarly following the allylic substitution reaction with other malonate derivatives.28-30... 

As alluded to above, this version of the Jt-allyl palladium reaction uses an allylic acetate or chloride. The use of the acetate is more common because acetate is a much weaker nucleophile than chloride. When it involves a substrate where diastereomeric products can result, the stereochemistry of the nucleophilic displacement is an important issue. Palladium assisted alkylation proceeds with net retention of configuration of the acetate or chloride, as seen in the conversion of 375 to 376.223e,f... 

In the Mitsunobu reaction with the allylic alcohols [2] and [5a,b] as with the palladium(0)-catalyzed reaction, good yields are obtained for the monomers [23] and [27] with an excess of nucleophile [22]. The dimers [24] and [28], however, ean be prepared only in moderate yields. Beeause the reaction does not proeeed via a n-allyl palladium complex with two reaetion sites, additional isomers are not produeed in this reaction. The conversion of [2] therefore yields only [27] and [28] as product. 

A five-component cascade reaction in which the last step is the trapping of a Tr-allyl-palladium species with a nucleophile such as piperidine, pyrrolidine, morpholine, and NaBPh4 afforded benzocyclopentenone derivatives 68 (Scheme 25). ... 

MBH diene adducts have also been employed successfully in a palladium-catalyzed asymmetric allylic alkylation reactions with various phenols in good regio- and enantioselectivity. These high enantioselectivities are even more substantial considering the ambiguity introduced by the additional double bond in the allylic system (Scheme 3.139). ... 

Four reviews on allylic substitution reactions have been published. The first deals with the enantioselective allylic substitutions by carbon nucleophiles, in the presence of both palladium and non-palladium catalysts. The second reviews stere- 0 oselective allylic substitution reactions forming asymmetric C-C, C-N, and C-O bonds. The third review covers new developments in metal-catalysed asymmetric 0 allylic substitution reactions with heteroatom-centred nucleophiles. Several applications of this new methodology are included. Finally, the catalytic 5 2 and 5 2 reactions of allylic alcohols, most of which occur with a very high ee, have been reviewed. ... 

The hydroboration of 1,3-dienes has also been reported, and these reactions generate Z-allylic boronic ester products. These reactions have been reported with palladium catalysts and are thought to occur through Tr-allyl intermediates. Reactions with butadiene and isoprene, followed by addition of the product to benzaldehyde, are shown in Equation 16.47. This equation also shows the presumed mechanism that proceeds by generation of a palladium allyl from the combination of diene and palladium hydride formed by oxidative addition of the borane. 

Transmetallation of (ri -allyl)palladium complexes with arylstannanes gives aryl-allylpalladium complexes 78 (Scheme 1.45) [366]. The reductive elimination from these complexes is slow and controls the reaction outcome. In order to produce an efHcient coupling, the coordination of p-benzoquinone or other electron-deficient alkenes to form 79 promotes the reductive elimination. Under catalytic conditions, the allyl electrophile acts as the electron-deficient alkene itself [366]. 

Palladium-catalyzed Allyllation Reactions. Palladium-catalyzed asymmetric allylic substitutions by soft nucleophiles are an extensively studied research area in organic chemistry with huge advances in ligand development and enantiocontrol seen in the past two decades. A typical asymmetric allylic substitution reaction with malonate is shown in eq 29. Diastereo- and enan-tioselective allylation of substituted nitroalkanes has also been reported. BSA has been used as a standard base in these reactions and functions satisfactorily. 

Phenols have been documented to serve as a versatile class of 0-nucleophiles in asymmetric allylic alkylation events. Even a sterically hindered ortho-disubstituted phenol such as 59 participated in a palladium-catalyzed allylic displacement reaction with carbonate 60 (Scheme 14.12) [69]. Product 62 was obtained in 88% ee and subsequently converted into (-)-galantha-mine (63), a selective inhibitor of acetylcholinesterase with potential in the treatment of Alzheimer s disease [69, 70). 

Hard carbon nucleophiles of organometallic compounds react with 7r-allyl-palladium complexes. A steroidal side-chain is introduced regio- and stereo-selectively by the reaction of the steroidal 7T-allylpalladium complex 319 with the alkenylzirconium compound 320[283]. 

Addition of several organomercury compounds (methyl, aryl, and benzyl) to conjugated dienes in the presence of Pd(II) salts generates the ir-allylpalladium complex 422, which is subjected to further transformations. A secondary amine reacts to give the tertiary allylic amine 423 in a modest yield along with diene 424 and reduced product 425[382,383]. Even the unconjugated diene 426 is converted into the 7r-allyllic palladium complex 427 by the reaction of PhHgCI via the elimination and reverse readdition of H—Pd—Cl[383]. 

Allenes also react with aryl and alkenyl halides, or triflates, and the 7r-allyl-palladium intermediates are trapped with carbon nucleophiles. The formation of 283 with malonate is an example[186]. The steroid skeleton 287 has been constructed by two-step reactions of allene with the enol trillate 284, followed by trapping with 2-methyl-l,3-cyclopentanedione (285) to give 286[187]. The inter- and intramolecular reactions of dimethyl 2,3-butenylmalonate (288) with iodobenzene afford the 3-cyclopentenedicarboxylate 289 as a main product) 188]. 

Based on the above-mentioned stereochemistry of the allylation reactions, nucleophiles have been classified into Nu (overall retention group) and Nu (overall inversion group) by the following experiments with the cyclic exo- and ent/n-acetales 12 and 13[25], No Pd-catalyzed reaction takes place with the exo-allylic acetate 12, because attack of Pd(0) from the rear side to form Tr-allyl-palladium is sterically difficult. On the other hand, smooth 7r-allylpalladium complex formation should take place with the endo-sWyWc acetate 13. The Nu -type nucleophiles must attack the 7r-allylic ligand from the endo side 14, namely tram to the exo-oriented Pd, but this is difficult. On the other hand, the attack of the Nu -type nucleophiles is directed to the Pd. and subsequent reductive elimination affords the exo products 15. Thus the allylation reaction of 13 takes place with the Nu nucleophiles (PhZnCl, formate, indenide anion) and no reaction with Nu nucleophiles (malonate. secondary amines, LiP(S)Ph2, cyclopentadienide anion). 

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

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