Palladium enolates allylation

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]... 

Preparation of palladium enolates and their reactions (/3-hydride elimination to enones, migratory insertion to C-C multiple bonds, reductive coupling with allyl or aryl groups, etc.) have been reported. However, the nucleophilic addition of palladium enolates to C=0 and C=N bonds has been little investigated.463... 

The first iridium catalysts for allylic substitution were published in 1997. Takeuchi showed that the combination of [fr(COD)Cl]2 and triphenylphosphite catalyzes the addition of malonate nucleophiles to the substituted terminus of t -allyliridium intermediates that are generated from allylic acetates. This selectivity for attack at the more substituted terminus gives rise to the branched allylic alkylation products (Fig. 4), rather than the linear products that had been formed by palladium-catalyzed allylic substitution reactions at that time [7]. The initial scope of iridium-catalyzed allylic substitution was also restricted to stabilized enolate nucleophiles, but it was quickly expanded to a wide range of other nucleophiles. 

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). 

The Tsuji-Trost Reaction (or Trost Allylation) is the palladium-catalyzed allylation of nucleophiles such as active methylenes, enolates, amines and phenols with allylic compounds such as allyl acetates and allyl bromides. 

A regio- and enantio-selective palladium-catalysed allylic alkylation of ketones has been reported, using allyl enol carbonate chemistry in which a CO2 unit tethers the allylating agent to the nucleophile.198... 

Palladium catalysed allylation of ordinary ketone and aldehyde enolates... 

Three new chirality centers are formed with high enantio- and complete diastereoselectivity in the course of the reaction of the enol triflate 37 to the bicyclo [3.3.0]octane derivative 38 (Scheme 11) [15]. In this transformation, the intermediate 39, formed by oxidative addition, leads to the cationic palladium-7r-allyl complex 40, which is finally converted to the isolated product 38 by regio- and diastereoselective nucleophilic addition of an acetate anion. The bicyclic product 38 is of interest as a building block for the synthesis of capnellene sesquiterpenes. 

Fig. 9. (A) A Pd-enolate complex observed by ESI(+)-MS during the palladium-catalyzed allylic substitution of l-acetoxy-l,3-diphenylpropene by acetylacetone 15. (B) A Pd-allyl complex observed by ESI(+)-MS during the palladium-catalyzed substitution of allylic acetates with sodium para-toluenesulfonate 20. ...

An intramolecnlar palladium-mediated allylic alkylation via a ketone enolate of piperidinone 54 was reported by Williams and coworkers for the synthesis of R)-l-hydroxyquinine 57 (eqnations 17 and 18) °. The key step involves a palladium-mediated Sjv2 -type cyclization reaction of enol ether 55 in the presence of BnsSnF, giving rise to a quinuclidine ketone, which was immediately rednced to 56 to avoid equilibration and /3-elimination. Interestingly, none of the undesired C3-vinyl stereoisomer was observed. 

The great importance of nonproteinogenic amino acids including a-substituted derivatives led to numerous investigations of modified amino acid enolates as nucleophiles in both classical alkylation or Mannich reactions and palladium-catalyzed allylic alkylations. 

Najera and coworkers introduced a new class of cyclic alanine templates (227, equation 59), the structure of which was anchored on Schollkopf s bislactim ether . Palladium-catalyzed allylations of the chiral pyrazinone derivative 227 with allylic carbonates (228) as substrates led to the formation of y,i5-unsaturated amino acids (229a-c) under very mild and neutral reaction conditions, whereas the required base for enolate preparation has been generated in situ from the allylic carbonate during jr-allyl complex formation. With this protocol in hand, the alkylated pyrazinones 229 were obtained with excellent regio- and diastereoselectivities (>98% ds). Finally, hydrolysis with 6 N aqueous HCl under relatively drastic conditions (150 °C) led to the free amino acids. 

These peptide enolates could also be used as excellent nucleophiles in palladium-catalyzed allylic alkylations. Reactions of numerous dipeptides (e.g. 263) with different allylic substrates (e.g. 264) and [AllPdClja as catalyst delivered (S,/f)-configured peptides with y,5-unsaturated side chains (265), usually in high yields and diastereoselectivities (equation 69). 

Braum M, Meier T. New developments in stereoselective palladium-catalyzed allylic alkylations of preformed enolates. 

Z)-2-butenylene dicarbonate with dimethyl malonate gives a low yield (20—40%) of 2-vinylcyclopropane-l,l-dicarboxylate with up to 70% ee (Scheme 2-38) [54], Reaction with methyl acetoacetate or acetylacetone takes place in a different manner to give a dihydrofuran derivative (59% ee), which results from nucleophilic attack of enolate oxygen at the cyclization step, (c) Asymmetric elimination of an acetyl-acetate ester gives (R)-4-rerr-butyl-l-vinylcyclohexene of up to 44% ee (Scheme 2-39) [55]. (d) Palladium-catalyzed allylic silylation is also applied to asymmetric synthesis... 

Palladium-catalyzed allylation and related reactions of enolates. 19... 

The use of C2-symmetric aziridines as chiral auxiliaries has been reviewed by Tanner <94AG(E)599>. Chiral A-acylaziridines such as (143) have been used in enolate chemistry (see Section 1.01.8.2). Aziridine-containing ligands such as (144) have been used for a variety of metal-catalyzed reactions such as the asymmetric dihydroxylation of alkenes, the palladium-catalyzed allylation of nucleophiles, asymmetric cyclopropanation, and aziridination <94AG(E)599,94TL4631). 

Scheme 4.4 details a short synthesis by Trost of an intermediate employed in the Gerlach synthesis of 9. ° Protected aldol 19 was reacted with a-lithio ethyl vinyl ether and the resulting alkoxide intermediate acylated to provide the protected diol 20 in 75% yield. Chain extension by way of a palladium-mediated allylic displacement with isopropyl phenylsulfonylacetate followed by ester exchange afforded a 62% yield of 21. Hydrolysis of the enol ether and 3-elimination of the sulfonyl group produced 22 in 66% yield. Ketalization of 22 then gave 16, which had been previously converted to the natural product in 50% yield. 1 ... 

The Wacker reaction provides a method for the preparation of 1,4-dicarbonyl compounds, by formation of an enolate, allylation with an allyl halide, followed by palladium-catalysed oxidation of the terminal alkene. The product 1,4-dicarbonyl compounds can be treated with base to promote intramolecular aldol reaction (Robinson annulation - see Section 1.1.2) to give cyclopentenones. Thus, in a synthesis of pentalenene, Wacker oxidation of the 2-aUyl ketone 115 gave the 1,4-diketone 116, which was converted to the cyclopentenone 117 (5.115). ... 

Transition Metal-catalyzed Allylic Alkylation. Simple ketone enolates were found to be suitable nucleophiles for palladium-catalyzed allylic alkylations. The palladium-catalyzed asymmetric allylic alkylation of a-aryl ketones will take place in the presence of NaHMDS and allyl acetate to produce the desired a,a-disubstituted ketone derivative in high yields andee (eq 16). ... 

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