Enolate palladium

In the prostaglandin synthesis shown, silyl enol ether 216, after transmetaJ-lation with Pd(II), undergoes tandem intramolecular and intermolecular alkene insertions to yield 217[205], It should be noted that a different mechanism (palladation of the alkene, rather than palladium enolate formation) has been proposed for this reaction, because the corresponding alkyl enol ethers, instead of the silyl ethers, undergo a similar cyclization[20I],... 

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]... 

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. 

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... 

Sodeoka and co-workers have reported enantioselective aldol and Mannich reactions (Equations (106) and (J07)) 464,464a 464e Involvement of palladium enolates was confirmed by 111 NMR and ESI-MS spectrometry. /3-Keto esters (pronucleophiles) directly add to imines with high selectivity without preformation of silicon enolates (Equation (108)). 

Addition of ketene silyl acetals to aldehydes and ketones is also mediated by achiral palladium(ll) acetate-diphosphine complexes (Equation (109)).46S,46Sa Although the precise mechanism is still unclear, high catalytic activity may be ascribed to the intermediacy of palladium enolates. 

In relation to palladium enolates, Yamamoto and co-workers reported palladium-catalyzed addition of malononi-trile derivatives to imines or aldehydes (Equation (110)).466,466a Oxidative addition of the C-H bond of the malononitrile to Pd(0) followed by insertion of an electrophile is proposed. 

Aldol reactions of silyl enolates are promoted by a catalytic amount of transition metals through transmetallation generating transition metal enolates. In 1995, Shibasaki and Sodeoka reported an enantioselective aldol reaction of enol silyl ethers to aldehydes using a Pd-BINAP complex in wet DMF. Later, this finding was extended to a catalytic enantioselective Mannich-type reaction to a-imino esters by Sodeoka s group [Eq. (13.21)]. Detailed mechanistic studies revealed that the binuclear p-hydroxo complex 34 is the active catalyst, and the reaction proceeds through a palladium enolate. The transmetallation step would be facilitated by the hydroxo ligand transfer onto the silicon atom of enol silyl ethers ... 

An important modification of the initial protocol has been introduced by Larock ef al. to afford indanones. The saturated ring results from the termination of the process by protonolysis of palladium enolate, which is likely to be generated from reversible palladium hydride elimination-addition. Proton source required for protonolysis hypothetically comes from adventitious water coming with hygroscopic chloride or solvent (Scheme 13). ... 

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 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 mechanism of the trimethylsilyl enol ether cyclization may involve formation of a palladium enol-ate which adds to the double bond. However, another mechanism is also possible involving attack of a palladium(II)-alkene complex upon the silyl enol ether double bond. 

In 1998, a new type of Pd(II) binuclear complex was reported which was effective for Mannich reactions of an imine derived from glyoxylate and anisidine with silicon enolates [38,39]. In these reactions, use of solvents including a small amount of water was essential. It was shown that water played an important role in this system water not only activated the Pd(II) complex to generate a cation complex, but also cleaved the N-Pd bond of the intermediate to regenerate the chiral catalyst. This reaction reportedly proceeded via an optically active palladium enolate on the basis of NMR and ESIMS analyses. A unique binuclear palladium-sandwiched enolate was obtained in the reaction of the p-hydroxo palladium complex with the silyl enol ether [(Eq. (9)]. 

Palladium enolate chemistry has been exploited to perform a range of catalytic enantioselective reactions on carbonyl substrates, including aldol, Michael, Mannich-type, and a-fluorination.154... 

Scheme 5. Formation of a chiral palladium enolate in Sodeoka s reaction.

NMR-spectroscopic analysis led to the postulation of a mechanism [13] (Scheme 7) involving the formation of a palladium enolate. 

The neutral palladium(II) compound 43 is transformed by addition of AgOTf into the cationic complex 44. In the presence of water an exchange of the triflate anion to hydroxide occurs (44 — 45). Finally, the palladium enolate 46 is formed from the palladium complex and the silyl enol ether. 

As far as late-transition elements are concerned, it is worthwhile to discuss some reactions occurring at C-bonded nickel and palladium enolates. Treatment of the nickel complex 73, derived from the afkynylenone 72 and Ni(cod)2, with dry dioxygen yielded the [3.1.0]bicyclohexane derivative 75 (equation 50), with the carbene species 74 as possible intermediate. ... 

Enantioselective fluorination reactions catalyzed by chiral palladium enolate complexes have been the subject of considerable research . For instance, the fluorination of acyclic /S-ketoester (88, equation 24) using Af-fluorobenzenesulfonimide (NFSI) gave product 89 in high yields and with excellent enantioselectivity (ee up to 94%) . This reaction can be carried out in environmentally benign alcoholic solvents and provides valuable synthetic building blocks that find applications in medicinal chemistry, chemical biology and material sciences. 

Palladacycles have also been characterized by IR spectroscopy <20050M945>. Thus, to provide insight into the bonding mode of palladium enolates in complexes 28-30, IR spectroscopic analyses were performed by Lu et al. They revealed z/(C=0) bands at 1687, 1676, and 1676cm for compounds 28, 29, and 30, respectively. 

Aside from 8, 7, 6-endo, and 8, 7, 6-exo Heck cyclizations, 5-exo Heck cyclization is also feasible, although 5-endo cyclization is not favored. Kurihara et al. revealed a 5-exo Heck cyclization in their synthesis of the indole analog of magallanesine [IOS]. As depicted in Scheme 39, 5-exo Heck cyclization converted substrate 224 into 225, the indole analog of magallanesine (226) in 28% yield. The intermediate of the vinylic substitution was a palladium enolate, which underwent a syn 3-hydride elimination after isomerization. 

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