Malonate palladium complexes

Nucleophilic Substitution of xi-Allyl Palladium Complexes. TT-Allyl palladium species are subject to a number of useful reactions that result in allylation of nucleophiles.114 The reaction can be applied to carbon-carbon bond formation using relatively stable carbanions, such as those derived from malonate esters and (3-sulfonyl esters.115 The TT-allyl complexes are usually generated in situ by reaction of an allylic acetate with a catalytic amount of fefrafcz s-(triphenylphosphine)palladium... 

The a-arylation of carbonyl compounds (sometimes in enantioselective version) such as ketones,107-115 amides,114 115 lactones,116 azlactones,117 malonates,118 piperidinones,119,120 cyanoesters,121,122 nitriles,125,124 sul-fones, trimethylsilyl enolates, nitroalkanes, esters, amino acids, or acids has been reported using palladium catalysis. The asymmetric vinylation of ketone enolates has been developed with palladium complexes bearing electron-rich chiral monodentate ligands.155... 

Based on these reactions, Imada et al. reported the first enantioselective alkylation of 2,3-alkadienyl phosphates 96 by employing malonate derivatives 97 in the presence of palladium complex catalysts bearing MeOBIPHEP or BINAP as ligand (Scheme 14.21) [49]. The highest enantioselectivity (90% ee) was obtained by the catalyst combination Pd2(dba)3-CHC13 and (R)-MeOBIPHEP. 

Ceric ammonium nitrate promoted oxidative addition of silyl enol ethers to 1,3-butadiene affords 1 1 mixtures of 4-(/J-oxoalkyl)-substituted 3-nitroxy-l-butene and l-nitroxy-2-butene27. Palladium(0)-catalyzed alkylation of the nitroxy isomeric mixture takes place through a common ij3 palladium complex which undergoes nucleophilic attack almost exclusively at the less substituted allylic carbon. Thus, oxidative addition of the silyl enol ether of 1-indanone to 1,3-butadiene followed by palladium-catalyzed substitution with sodium dimethyl malonate afforded 42% of a 19 1 mixture of methyl ( )-2-(methoxycarbonyl)-6-(l-oxo-2-indanyl)-4-hexenoate (5) and methyl 2-(methoxycarbonyl)-4-(l-oxo-2-indanyl)-3-vinylbutanoate (6), respectively (equation 12). 

No reaction of soft carbon nucleophiles takes place with propargylic acet-ates[37], but soft carbon nucleophiles, such as /7-keto esters and malonates, react with propargylic carbonates under neutral conditions using dppe as a ligand. The carbon nucleophile attacks the central carbon of the ir-alleny[palladium complex 81 to form the 7r-allylpalladium complex 82, which reacts further with the carbon nucleophile to give the alkene 83. Thus two molecules of the a-monosubstituted /7-keto ester 84, which has one active proton, are... 

Dicarboxylic acids form monomeric complexes with palladium(II), K2[Pd(X2)2] (X2 = oxalate, malonate, etc,).153154 They may be prepared by warming a suspension of palladium(II) chloride with a concentrated solution of the alkali metal dicarboxylate or by using other palladium complexes containing readily substituted ligands such as [Pd(OH)2], [Pd(N03)2(H20)2] or [Pd(02CMe)2]3-155 These complexes are claimed to have useful antitumour properties.155 Complexes [Pd(X2)L2] (X2 = dicarboxylate L = amine or L2 = diamine) may be prepared by reaction of the dichloro complex with a carboxylate salt.156,128... 

Stereoselective allylic alkylations have been carried out with the aid of palladium catalysts. The 17-(Z)-ethylidene groups of steroids (obtained from the ketones by Wittig olefination) form n-allyl palladium complexes in the presence of copper(n) salts (B.M. Trost, 1974, 1976). Their alkylation with dimethyl malonate anions in the presence of 1,2-ethane-diylbis[diphenylphosphine] (— diphos) gives a reaction exclusively at the side chain and only the (20S) products. If one starts with the endocyclic 16,17 double bond and replaces an (S)-20-acetoxy group by using tetrakis(triphenylphospbine)palladium,the substitution occurs with complete retention of configuration, resulting from two complete inversions (B.M. Trost, 1976). 

A spectacular application allowed the synthesis of fenestranes by a three-step sequential action of cobalt nanoparticles and a palladium catalyst [131]. The cascade reaction started with a PKR of enyne 105, accomplished by the cobalt catalyst giving 106, followed by the formation of allyl-7r3 palladium complex 107 which reacted with a nucleophile derived from diethyl malonate, to give enyne 108. The final step was a second PKR that gave 109 in good yield. They used cobalt nanoparticles as with Co/charcoal the third step did not take place, apparently due to damage in this catalyst after the allylation step (Scheme 31). 

Reaction of the palladium complex of ligand la with 10a in the presence of Af,0-bis(trimethylsilyl)acetamide (BS A), catalytic KOAc as the base, and dimethyl malonate results in good yield and high selectivities for 12a (eq 4). The most efficient ligand in terms of regio- and enantioselectivity is la. In benzene, the regio-and enantioselectivity are further improved (Table 1). 

Substitution reactions of allylic substrates with nucleophiles have been shown to be catalyzed by certain palladium complexes [2, 42], The catalytic cycle of the reactions involves Jt-allylpalladium as a key intermediate (Scheme 2-22). Oxidative addition of the allylic substrate to a palladium(o) species forms a rr-allylpal-ladium(n) complex, which undergoes attack of a nucleophile on the rr-allyl moiety to give an allylic substitution product. The substitution reactions proceed in an Sn or Sn- manner depending on catalysts, nucleophiles, and substituents on the substrates. Studies on the stereochemistry of the allylic substitution have revealed that soft carbon nucleophiles represented by sodium dimethyl malonate attack the TT-allyl carbon directly from the side opposite to the palladium (Scheme 2-23). 

Following the usual mechanism (pp. 1330-4), the palladium complexes to the face of the alker.e opposite the bridge and the ester group leaves to give an allyl cation complex. This is attacked by the malonate anion from the opposite face to the palladium. So the overall resrdt is retention, the starting material giving the cis product. 

Similarly, palladium complexes 22 obtained via nucleophilic adddition of malonate carbanions to norbornadienepalladium complexes, gave the corresponding nortricyclenones 24. °... 

A multi-step asymmetric synthesis of a hydrindane framework was achieved in water via asymmetric allylic alkylation, propargylation and aquacatalytic cycloisomerization of a 1,6-enyne, where all three steps were performed in water with the recyclable polymeric catalysts. The racemic cyclohexenyl ester 27 reacted with diethyl malonate under the conditions mentioned in Table 6.1 to give 90-92% ee of 34b. The polymeric chiral palladium complex 23-Pd was reused four times... 

Binap 3.43 is also a good ligand for palladium complexes. Although 71-allyl palladium-binap complexes have met limited applications in asymmetric allylation of malonate like derivatives [872], binap-PdCl2 complexes induce enantioselective Heck reactions [902] and 1,4-disilylations of a-enones [903],... 

Asymmetric alkylations can be performed in the presence of catalytic amounts of chiral phase transfer catalysts or through the intermediacy of 7t-allyl-palladium complexes bearing chiral ligands. Both methods normally require relatively acidic carbon acids (pKa 5 17) such as (3-diketones, P-keto- or cyanoesters or malonic acid derivatives. 

Other Reactions of Unsaturated Steroids.—A review on organopalladium intermediates includes several steroidal examples. A mechanistic study of the formation of the 7r-allyl palladium complex (65) from the corresponding 3-oxocholest-4-ene led to the conclusion that initial 7r-complexing was rate limiting. Reactions of a series of similar ir-allyl palladium complexes (66)—(68) with dialkyl malonate ion gave the 3-oxo-A -6/S-yl malonates (69)—(71) respec-... 

On the other hand, Tsuji, Morikawa, and Takahashi found that ir-allyl palladium complexes react with nucleophiles, such as amines and enamines, and active methylene compounds, such as malonates, with reduction of bivalent palladium to the zero-valent metal 39>4o). This is due to the stability of the reduced species. 

The product of the palladation reaction exists as an active intermediate and cannot be isolated in general. However, the product of palladation was isolated as a stable compound in the reaction of cyclooctadiene palladium complex with carbanions such as malonate or alcoholate. Further reaction of the complex with base to give bicyclo (6,1,0) nonene and bicyclo (3,3,0) octane systems was reported by Takahashi and Tsuji 108>. The reactions are understood as intra-and intermolecular nucleophilic addition reactions. 

They have presented a further library synthesis of phosphines which show very different properties in catalysis to those above. A library of phosphines 98 was prepared based on the well-known /3-turn forming motif -Pro-D-Yyy-(where Yyy is a D-amino acid) with the phosphine-containing amino acids flanking this element.The structural features that were varied in the initial library prepared were the amino acids at the N- and C-termini and substitutions of D-amino acids next to the proline of the -Pro-D-Yyy- fragment. Palladium complexes of the library members were formed on the pins from [PdCl(77 -C3Hs)]2 and these screened for catalytic activity in the asymmetric addition of dimethyl malonate to cyclopentenyl acetate (Scheme 49). The selectivities obtained ranged from 34% ee for the... 

Gagn6 et al. developed polymer active sites that additionally contained a receptor (recognition sites) displayed in the outer sphere of the metal center (reactive site). The Suzuki reaction of /)-bromoanisole with phenyl boronic acid and the allylation of dimethyl malonate with allyl acetate were both chosen to assess the presence and/or effect of the crown-ether in crown-ether-molecular imprinting polymer-palladium complex. The results showed that molecular imprinting can be used to functionalize the second-coordination sphere of a transition metal complex and subsequently affect its catalytic behavior. 

Initial reactions with n-allyl palladium complexes involved treatment of this stabilized cation with nucleophiles. Trost found that 355 reacted with diethyl sodiomalonate in the presence of triphenylphosphine (PPh3). The phosphine acted as a basic ligand and coordinated with the palladium. The major product from reaction with sodium malonate was 356, formed in 68% yield.220 This reaction completes the initially set goal (in... 

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