Enolate allylpalladium

The silyl enol ethers 209 and 212 are considered to be sources of carbanions. and their transmetallation with Pd(OAc)2 forms the Pd enolate 210. or o.w-tt-allylpalladium, which undergoes the intramolecular alkene insertion and. 1-elimination to give 3-methylcyclopentenone (211) and a bicyclic system 213[199], Five- and six-membered rings can be prepared by this reaction[200]. Use of benzoquinone makes the reaction catalytic. The reaction has been used for syntheses of skeletons of natural products, such as the phyllocladine intermediate 214[201], capnellene[202], the stemodin intermediate 215[203] and hir-sutene [204]. 

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]... 

Another preparative method for the enone 554 is the reaction of the enol acetate 553 with allyl methyl carbonate using a bimetallic catalyst of Pd and Tin methoxide[354,358]. The enone formation is competitive with the allylation reaction (see Section 2.4.1). MeCN as a solvent and a low Pd to ligand ratio favor enone formation. Two regioisomeric steroidal dienones, 558 and 559, are prepared regioselectively from the respective dienol acetates 556 and 557 formed from the steroidal a, /3-unsaturated ketone 555. Enone formation from both silyl enol ethers and enol acetates proceeds via 7r-allylpalladium enolates as common intermediates. 

The reductive coupling of the 7r-allylpalladium enolates 679 gives the allylated ketones. This reaction is also possible thermally, as the Carroll reaction, which... 

The decarboxylation of allyl /3-keto carboxylates generates 7r-allylpalladium enolates. Aldol condensation and Michael addition are typical reactions for metal enolates. Actually Pd enolates undergo intramolecular aldol condensation and Michael addition. When an aldehyde group is present in the allyl fi-keto ester 738, intramolecular aldol condensation takes place yielding the cyclic aldol 739 as a main product[463]. At the same time, the diketone 740 is formed as a minor product by /3-eIimination. This is Pd-catalyzed aldol condensation under neutral conditions. The reaction proceeds even in the presence of water, showing that the Pd enolate is not decomposed with water. The spiro-aldol 742 is obtained from 741. Allyl acetates with other EWGs such as allyl malonate, cyanoacetate 743, and sulfonylacetate undergo similar aldol-type cycliza-tions[464]. 

Addition of organopalladium species (aryl-, vinyl-, allylpalladium and palladium enolates) to C=0 and CN multiple bonds has enjoyed wide applications as the key step of various catalytic processes. 

Allyl esters of acetoacetates7-8-9-11 react with Pd° catalysts to generate initially a bisphosphine allylpal-ladium cation, with the 3-ketocarboxylate serving as counterion. Under the reaction conditions the (3-ketocarboxylate decarboxylates, yielding a -Tr-allylpalladium ketone enolate complex. The required nucleophile is thus formed in situ and is capable of Pd-mediated alkylation. A wide spectrum of reactions have been based on this chemistry which will be discussed in later sections. 

Initial reports on the use of simple enolates as nucleophiles in TT-allylpalladium chemistry met with only limited success.77 106 The enolate of acetophenone reacted with allyl acetate in the presence of Pd(PPh3)4, but gave predominantly dialkylated product.106 The use of the enol silyl ether of acetophenone gave only monoalkylated product with allyl acetate and Pd° catalysis, but substituted allyl acetates did not function in this reaction.106 Enol stannanes, however, have been found to give monoalkylated products with a wide variety of allyl acetates (equation 19).106 In situ generation of enol stannanes from lithium enolates and trialkylstannyl trifluoroacetates followed by Pd°-catalyzed allylation has been demonstrated.107... 

The addition of potassium enolates to preformed ir-allylpalladium complexes has also been reported.111... 

Considerable use has also been made of allyl carbonates as substrates for the allylation of Pd enolates.9 The reaction of Pd° complexes with allyl enol carbonates119,120 proceeds by initial oxidative addition into the allylic C—O bond of the carbonate followed by decarboxylation, yielding an allylpalladium enolate, which subsequently produces Pd° and the allylated ketone (equation 22). In like fashion, except now in an intermolecular sense, allyl carbonates have been found to allylate enol silyl ethers (equation 23),121 enol acetates (with MeOSnBu3 as cocatalyst) (equation 24),122 ketene silyl acetals (equation 25)123 and anions a to nitro, cyano, sulfonyl and keto groups.115,124 In these cases, the alkoxy moiety liberated from the carbonate on decarboxylation serves as the key reagent in generating the Pd enolate. 

Allyl carbamates (equation 26)125 and isoureas (equation 27)9S generate allylpalladium enolates by virtually identical mechanisms. 

Ketoacids126,127 form the same intermediates as the allyl 3-ketoesters by nucleophilic addition of the carboxylate to a n-allylpalladium complex. Decarboxylation generates the allylpalladium enolate, which again yields Pd° and allylated ketone. Enol silyl ethers have also been employed with allyl arsenites93 to provide allylated ketones. 

The enolates of esters or ketones again are envisioned to add to ir-allylpalladium intermediates in the second step of the proposed mechanism (Scheme 3X96... 

Oxa- Tr-allylpalladium complexes (10), which can also be envisioned as palladium enolates (11), are susceptible to (3-hydride elimination, and as such have been principally used in methodologies for the preparation of (3,(3-unsaturated carbonyl compounds. 

The mechanisms proposed for these reactions are all quite analogous, and only the intramolecular cases will be considered in detail (Scheme 5). Oxidative addition by Pd° into the allylic C—O bond of the allyl 0-ketocaiboxylate produces an allylpalladium caxboxylate. This species then undergoes decarboxylation to yield an allylpalladium enolate (oxa-ir-allyl), which subsequently eliminates a 0-H to form the enone and provide an allyl-Pd-H. Reductive elimination from the allyl-Pd-H yields propene and returns Pd to its zero oxidation state. A similar mechanism can be imagined for the alkenyl allylcarbonate. Oxidative addition by the Pd° forms an allylpalladium carbonate, which decarboxylates again to give an allylpalladium enolate (oxa-ir-allyl). 0-Hydride elimination and reductive elimination complete the process. The intermolecular cases derive the same allylpalladium enolate intermediates, only now as the result of bimolecular processes. 

The biologically significant a-methylene ketones have been prepared by a similar strategy, entailing a Pd°-catalyzed decarboxylation-deacetoxylation of allyl-a-acetoxymethyl 0-ketocarboxylates. The crucial allylpalladium enolate now 0-eliminates OAc rather than H (equation 143).368... 

Tin enolates add to rr-allylpalladium complexes directly on the allyl ligand (inversion).106 383 Therefore, in tandem with the inversion of configuration incurred in the oxidative addition of a Pd° catalyst into an allyl acetate, a net overall retention is observed (equation 155). 

The reaction of 3-ketoacids with allyl carboxylates is also believed to proceed via a palladium enolate intermediate.126 Less than complete stereospecificity is also observed in these reactions (equation 163). Interestingly, the bicyclic lactone substrate employed to ascertain the stereointegrity of this reaction, in addition to being incapable of any syn-anti isomerization, cannot epimerize the starting material by car-boxylate attack at the metal. The observed stereochemical leakage could be due to epimerization of the intermediate allyl complex (equation 164) or reductive elimination of an allylpalladium enolate (retention) (equation 165). 

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