Palladium trifluoroacetate

In the synthesis of morphine, bis-cyclization of the octahydroisoqtiinolinc precursor 171 by the intramolecular Heck reaction proceeds using palladium trifluoroacetate and 1,2,2,6,6-pentamethylpiperidine (PMP). The insertion of the diene system forms the rr-allylpalladium intermediate 172, which attacks the phenol intramolecularly to form the benzofuran ring (see Section 1.1.1.3). Based on this method, elegant total syntheses of (-)- and (+ )-dihydrocodei-none and (-)- and ( + )-morphine (173) have been achieved[141]. 

The 2-alkylideneindanone 282 is formed by carbopalladation via ring expansion of the alkynylcyclobutenol 280 with palladium trifluoroacetate to yield an intermediate 281 and its protonolysis. 4-Oxygenated 5-alkylidenecyclopente-nones react similarly[139]. 

Oxidation of alkenes and dienes involving an allene substituent as a formal nucleophile is a conceptually new reaction. Allcnc-substitutcd 1,3-cyclohexadienes 34 undergo a pal-ladium(II)-catalyzed oxidation to give bicydic compounds 35 or 36 in good yields (Scheme 17.14) [14]. When y-alkenylallenes, e.g. 37, 41 and 43, were treated with 1 mol% palladium trifluoroacetate, a similar oxidative carbocyclization took place [15]. In both reactions the new stereocenters are formed with high stereoselectivity. 

Acetoxylation of propene to allyl acetate can be performed in the liquid phase with high selectivity (98%) in acetic acid in the presence of catalytic amounts of palladium trifluoroacetate. The stability and activity of this catalyst can be considerably increased by adding copper (II) trifluoroacetate and sodium acetate as cocatalysts (100 °C, 15 bar, reaction time = 4 h, conversion = 70%, selectivity = 97%). Gas-phase procedures for the manufacture of allyl acetate are described in several patents and use conventional palladium catalysts deposited on alumina or silica, together with cocatalysts (Au, Fe, Bi, etc.) and sodium acetate. The activity and selectivity reported for these catalysts are very high (100-1000 g l-1 h-1, selectivity = 90-95% ).427 A similar procedure has been used for the synthesis of methallyl acetate from 2-methylpropene.428... 

One of the first significant advances in the chemistry of TT-allylpalladium complexes was the discovery that alkenes could be directly converted into the corresponding allyl complex by substitution into the allylic C—H bond. A variety of recipes have now been reported that can accomplish this transformation. Initially, palladium chloride17-23 or its more soluble forms, sodium or lithium tetrachloropalladate24-27 and bisacetonitrile palladium dichloride,28-30 in alcohol or aqueous acetic acid solvent were employed. The use of palladium trifluoroacetate, followed by counterion exchange with chloride, represents the mildest and most effective means available to accomplish this reaction.31... 

In the presence of palladium(II) and silver(I) salts, arene carboxylates could be converted to aryl palladium species, which were engaged in Heck coupling reactions.90 Since the more electrophilic palladium trifluoroacetate proved to be the bestcatalyst, decarboxylation probably occurred by aromatic electrophilic substitution... 

Allylic trifluoroacetates are very reactive with Pd reagents, generating -allyl palladium trifluoroacetates (equation 51), which can react further to produce cationic 7r-aUyl complexes when reacted with chelating amines (equation 52). The cationic complexes can also be synthesized from ly -dWyl palladium trifluoroacetates by treatment with HBF4 and ligands, L, producing PdL2( -allyl)+ BF4 complexes. 

Heck reactions in SC-CO2 were performed on REM resin. Palladium trifluoroacetate (10 mol%) in conjunction with DIPEA gave the highest yields at only 40 °C. Aryl bromides gave somewhat lower yields than aryl iodides [42]. 

An in situ catalyst formed from palladium acetate and the perfluoroalkyl-substituted ligand [F(CF2)6(CH2)2 2PPh resulted in the formation of methylcin-namate in 91 % isolated yield after 64 h at 100 °C and an estimated CO2 density of ca. 0.7 g mL [62]. The ligand 3,5-H°F -tpp gave almost identical yield after 24 h at 90 °C under otherwise very similar conditions [63]. Tris(2-furyl)phos-phine also lead to active catalysts [63], especially when used together with fluorinated Pd-sources like palladium trifluoroacetate [64]. Most of the above systems lost their activity if metallic palladium was formed under non-optimum reaction conditions. However, the use of a commercial heterogeneous Pd/C catalyst was reported to give up to 85% yield of methyl cinnamate in the presence of CO2 at temperatures and pressures beyond the critical data [65]. The CO2 density in the latter experiments can be estimated to ca. 0.22 g mL" and was... 

The nature of the anion can also influence whether vinylic or allylic oxidation predominates. For example, with palladium trifluoroacetate allylic oxidation occurs even in the absence of a base [12]. The two different path way s-ally lie and vinylic substitution-are illustrated in Figure 2. 

In agreement, palladium trifluoroacetate anion reacts rapidly with olefins under mild conditions to yield 7t-allylpalladium complexes ... 

It is interesting that ethane can be converted to propionic acid and its mixed anhydride and trifluoromethyl ethyl ketone under the action of hydrogen peroxide in trifluoroacetic anhydride at 80 °C in the absence of a metal compound [49], The addition of palladium trifluoroacetate resulted in simple oxidation to ethanol and acetaldehyde. 

Meyers et al. reported that arylpalladium intermediates are generated from electron-rich aromatic acids 88 by decarboxylation and undergo HR in 5 % DMSO-DMF when palladium trifluoroacetate was used. However, addition of 3 equivalents of Ag2C03, which may accelerate the decarboxylation, is necessary [58]. 

Allyl ketones are prepared by cross-coupling of allyl esters with acyl metals. For the coupling, allyl trifluoroacetate (306) and the acylstannane 307 were used to provide the ketone 308 [112]. Similarly, acylsilanes such as 310 are used for the coupling with allyl trifluoroacetate 309 to give 311 [113]. For these couplings, use of allyl trifluoroacetate is important. No reaction occurred with allyl acetate. While ligandless palladium trifluoroacetate is most effective, Pd(OAc)2 shows low activity. 

Various reactions of pronucleophiles with allenes has been reviewed by Yamamoto and Radhakrishnan [18]. Regioselectivity in these reactions is controlled by steric and electronic effects. The attack at C-3 is a main path, but several exceptional cases have been reported. Due to electronic bias, the hydrocarbonation of alkoxy- or phenoxyallenes 70 gives allylic ethers as the C-1 adduct 72 either exclusively or predominantly via 7r-allylpalladium 71 [19]. Trost expanded the regioselective formation of allylic ether to an asymmetric reaction. Addition of the Meldrum s acid 74 to the allenyl ether 73 catalyzed by palladium trifluoroacetate and (5, 5)-XIII-l as a chiral ligand in the presence of trifluoroacetic acid afforded the the allylic ether 75 with 99 % ee in 75 % yield [20]. 

There have been several reports of ortho-acylations using palladium catalysis. Orthoacylation of acetanilides with aldehydes is catalysed by palladium trifluoroacetate in the presence of f-butylhydroperoxide. A likely pathway involves the formation of a cyclopalladated intermediate (57), which reacts with an acyl radical to give (58) followed by carbon—carbon bond formation through reductive elimination. A similar methodology has been used in the preparation of a range of ort/io-acylacetanilides. ... 

While such a process had initially been observed as an undesired side-reaction in transformations where copper salts were employed as re-oxidants [13], Chemler demonstrated that various aminohalogenation reactions proceed in THF or acetonitrile in the presence of potassium carbonate as base [14]. These reactions employ palladium trifluoroacetate or palladium dibromide as catalyst source and require a moderate excess of the copper oxidant (3-4 equiv) giving moderate to excellent yields. However, they usually suffer from rather low selectivity, either in the initial aminopalladation or via subsequent rearrangement pathways to provide mixtures of pyrrolidines and piperazines (Scheme 4.2, Eq. (4.3)). A stoichiometric control reaction in the presence of palladium bromide led only to the Wacker cydization together with an alkene isomerization product, suggesting that the presence of copper(II) salts is crucial for the overall process. The exact role of the copper(II) salts has not yet been darified and palladium intermediates of different oxidation states may be involved in the final stage of carbon-halogen bond formation. 

Peroxide mechanisms are common in hydrocarbon oxidation. tert-Butyl hydroperoxide (BuOOH) can be used as an oxidizing agent with a palladium trifluoroacetate catalyst. The catalyst is [Pd(OCOCF3)(OOBu)], which adds to the alkene linkage to give 25. Decomposition of this intermediate to ketone... 

The second type of palladium intermediate is a rr-allyl complex of Pd(II). The TT-allyl complexes can be obtained from Pd(II) salts and allylic acetates, allyl ethers, and other allylic compounds having potential leaving groups.The same rr-allyl complexes can be prepared from alkenes by reaction with palladium chloride or palladium trifluoroacetate. " For unsymmetrical alkenes with more than one reactive allylic position, the latter method gives rise to mixtures of rr-allyl complexes. 

Synthesis of 66 A mixture of palladium trifluoroacetate (6.4 mg, 19.8 mmol) and (5,5)-Bn-BOXAX 65 (44.6 mg, 77.9 mmol) dissolved in CH2CI2 (0.1 mL, degassed) was stirred for 30 minutes at room temperature, then treated with p-benzo-quinone (84.9 mg, 0.785 mmol), and finally stirred for a further 10 minutes. A solution of 64 (60.4 mg, 0.195 mmol) and methyl vinyl ketone (90.4 mg, 0.975 mmol) dissolved in CH2CI2 (O.lOmL, degassed) was added, and the mixture was stirred at room temperature for 3 days (thin layer... 

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