Palladium formation

Formic acid behaves differently. The expected octadienyl formate is not formed. The reaction of butadiene carried out in formic acid and triethylamine affords 1,7-octadiene (41) as the major product and 1,6-octadiene as a minor product[41-43], Formic acid is a hydride source. It is known that the Pd hydride formed from palladium formate attacks the substituted side of tt-allylpalladium to form the terminal alkene[44] (see Section 2.8). The reductive dimerization of isoprene in formic acid in the presence of Et3N using tri(i)-tolyl)phosphine at room temperature afforded a mixture of dimers in 87% yield, which contained 71% of the head-to-tail dimers 42a and 42b. The mixture was treated with concentrated HCl to give an easily separable chloro derivative 43. By this means, a- and d-citronellol (44 and 45) were pre-pared[45]. 

Cleavage with palladium/formate [194[, other linkers [195[ for arenes]... 

The alkyne insertion reaction is terminated by anion capture. As examples of the termination by the anion capture, the alkenylpalladium intermediate 189, formed by the intramolecular insertion of 188, is terminated by hydrogenolysis with formic acid to give the terminal alkene 192. Palladium formate 190 is formed, and decarboxylated to give the hydridopalladium 191, reductive elimination of which gives the alkene 192 [81]. Similarly the intramolecular insertion of 193 is terminated by transmetallation of 194 with the tin acetylide 195 (or alkynyl anion capture) to give the dienyne 196 [82], Various heterocyclic compounds are prepared by heteroannulation using aryl iodides 68 and 69, and internal alkynes. Although the mechanism is not clear, alkenylpalladiums, formed by insertion of alkynes, are trapped by nucleophiles... 

As shown in Scheme 5.1, formic acid behaves differently to other carboxylic acids. Expected octadienyl formate is not formed. The reaction with formic acid in the presence of EtjN affords 1,7-octadiene (140) [62 64], The first step is the protonation of bis-Ji-allylpalladium 68 with formic acid to generate 167. Formic acid is a hydride source, ft is known that the Pd hydride, formed by the decarboxylation of palladium formate, attacks the substituted side of 7i-allylpalladium as shown by 167 to form the terminal alkene 140 [65], The regioselective attack of Pd—H at the more substituted side of 7r-allyl systems is covered in Section 4.3.7. 

L, used in this mechanism, is a ligand which can stabilize the intermediate palladium complexes and satisfy a coordination number of the palladium whatever it is. L, for example, can be carbon monoxide, phosphines, solvents, or another molecule of palladium. Formation of hydride complexes by the oxidative addition of hydrogen chloride or hydrogen to a metal complex is well known (9, 27), as is formation of alkyl metal complexes by addition of metal hydrides to olefins. 

Due to the higher reactivity of the allene moiety toward hydropalladation in 1,6-allenynes, the reaction may proceed via a hydropalladation of the allene moiety of 146 affording a vinylic palladium intermediate 147. Subsequent intramolecular carbopalladation of the C-C triple bond moiety would lead to the 1,3-dienyl palladium formate 148. Releasing of CO2 and reductive elimination afford the final product 149 and Pd(0). Pd(0) would react with HCO2H to afford HC02PdH, which is the catalytically active species (Scheme 61) [36]. 

In the palladium-catalyzed carbonylation process, allyl formate, prepared by the reaction of allyl alcohol with formic acid, oxidatively adds to Pd(0) species with the C-0 bond cleavage to give allyl palladium formate. The CO insertion into the allylpalladium bond produces butenoyl palladium formate, which reductively ehminates butenoic formic anhydride with regeneration of the catalytically active Pd(0) species. Spontaneous decarbonylation of the mixed anhydride yields 3-butenoic acid, which isomerizes to 2-butenoic acid [61]. The process to give the butenoic acid proceeds only under CO pressure, suggesting that the CO insertion into the allyl-Pd bond is favored under CO pressure. When the reaction is carried out under normal pressure of CO, decarboxylation of the formate to give palladium hydride takes place. Reductive elimination of the allylpalladium hydride yields hydrogenation product of the allyl moiety [62]. 

Formates. The decarboxylation reaction of metal formates is a fairly general route for the synthesis of metal hydrides and it has been applied to many transition metals. As an example, allyl palladium formates, which are believed to be intermediates in the catalytic reductive cleavage of allylic acetates and carbonates with formic acid to give monoolefins (Scheme 6.32), have been synthesized. In fact the complexes undergo decarboxylation and the reductive elimination of the allyl hydrido fragments, supporting the catalytic cycle proposed [105]. 

Aluminum Reagents. Alkenylalnminnm compounds can also be used as reagents for alkenylation in reactions promoted by palladium. Formation of a 2-alkenylpyridine 216 is shown (Scheme 82). 

Pd-catalyzed hydrogenolysis of allylic compounds with formates is an efficient and mild method. The most important feature of the hydrogenolysis is that the hydride generated from the palladium formate attacks the more substituted side of the allylic system to give less substituted olefins. Various terminal allylic compounds are converted to 1-alkenes. - ... 

Pd(II) compounds coordinate to alkenes to form rr-complexes. Roughly, a decrease in the electron density of alkenes by coordination to electrophilic Pd(II) permits attack by various nucleophiles on the coordinated alkenes. In contrast, electrophilic attack is commonly observed with uncomplexed alkenes. The attack of nucleophiles with concomitant formation of a carbon-palladium r-bond 1 is called the palladation of alkenes. This reaction is similar to the mercuration reaction. However, unlike the mercuration products, which are stable and isolable, the product 1 of the palladation is usually unstable and undergoes rapid decomposition. The palladation reaction is followed by two reactions. The elimination of H—Pd—Cl from 1 to form vinyl compounds 2 is one reaction path, resulting in nucleophilic substitution of the olefinic proton. When the displacement of the Pd in 1 with another nucleophile takes place, the nucleophilic addition of alkenes occurs to give 3. Depending on the reactants and conditions, either nucleophilic substitution of alkenes or nucleophilic addition to alkenes takes place. 

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],... 

In the reaction of aryl and alkenyl halides with 1,3-pentadiene (248), amine and alcohol capture the 7r-allylpalladium intermediate to form 249. In the reactions of o-iodoaniline (250) and o-iodobenzyl alcohol (253) with 1,3-dienes, the amine and benzyl alcohol capture the Tr-allylpalladium intermediates 251 and 254 to give 252 and 255[173-175]. The reaction of o-iodoaniline (250) with 1,4-pen tadiene (256) affords the cyclized product 260 via arylpalladiuni formation, addition to the diene 256 to form 257. palladium migration (elimination of Pd—H and readdition to give 258) to form the Tr-allylpalladium 259, and intramolecular displacement of Tr-allylpalladium with the amine to form 260[176], o-Iodophenol reacts similarly. 

Allenes also react with aryl and alkenyl halides, or triflates, and the 7r-allyl-palladium intermediates are trapped with carbon nucleophiles. The formation of 283 with malonate is an example[186]. The steroid skeleton 287 has been constructed by two-step reactions of allene with the enol trillate 284, followed by trapping with 2-methyl-l,3-cyclopentanedione (285) to give 286[187]. The inter- and intramolecular reactions of dimethyl 2,3-butenylmalonate (288) with iodobenzene afford the 3-cyclopentenedicarboxylate 289 as a main product) 188]. 

Based on the above-mentioned stereochemistry of the allylation reactions, nucleophiles have been classified into Nu (overall retention group) and Nu (overall inversion group) by the following experiments with the cyclic exo- and ent/n-acetales 12 and 13[25], No Pd-catalyzed reaction takes place with the exo-allylic acetate 12, because attack of Pd(0) from the rear side to form Tr-allyl-palladium is sterically difficult. On the other hand, smooth 7r-allylpalladium complex formation should take place with the endo-sWyWc acetate 13. The Nu -type nucleophiles must attack the 7r-allylic ligand from the endo side 14, namely tram to the exo-oriented Pd, but this is difficult. On the other hand, the attack of the Nu -type nucleophiles is directed to the Pd. and subsequent reductive elimination affords the exo products 15. Thus the allylation reaction of 13 takes place with the Nu nucleophiles (PhZnCl, formate, indenide anion) and no reaction with Nu nucleophiles (malonate. secondary amines, LiP(S)Ph2, cyclopentadienide anion). 

Ketones can be prepared by trapping (transmetallation) the acyl palladium intermediate 402 with organometallic reagents. The allylic chloride 400 is car-bonylated to give the mixed diallylic ketone 403 in the presence of allyltri-butylstannane (401) in moderate yields[256]. Alkenyl- and arylstannanes are also used for ketone synthesis from allylic chlorides[257,258]. Total syntheses of dendrolasin (404)f258] and manoalide[259] have been carried out employing this reaction. Similarly, formation of the ketone 406 takes place with the alkylzinc reagent 405[260],... 

Lithiation at C2 can also be the starting point for 2-arylatioii or vinylation. The lithiated indoles can be converted to stannanes or zinc reagents which can undergo Pd-catalysed coupling with aryl, vinyl, benzyl and allyl halides or sulfonates. The mechanism of the coupling reaction involves formation of a disubstituted palladium intermediate by a combination of ligand exchange and oxidative addition. Phosphine catalysts and salts are often important reaction components. 

The reaction is used for the chain extension of aldoses in the synthesis of new or unusual sugars In this case the starting material l arabinose is an abundant natural product and possesses the correct configurations at its three chirality centers for elaboration to the relatively rare l enantiomers of glucose and mannose After cyanohydrin formation the cyano groups are converted to aldehyde functions by hydrogenation m aqueous solution Under these conditions —C=N is reduced to —CH=NH and hydrolyzes rapidly to —CH=0 Use of a poisoned palladium on barium sulfate catalyst prevents further reduction to the alditols... 

Oxidative Carbonylation of Ethylene—Elimination of Alcohol from p-Alkoxypropionates. Spectacular progress in the 1970s led to the rapid development of organotransition-metal chemistry, particularly to catalyze olefin reactions (93,94). A number of patents have been issued (28,95—97) for the oxidative carbonylation of ethylene to provide acryUc acid and esters. The procedure is based on the palladium catalyzed carbonylation of ethylene in the Hquid phase at temperatures of 50—200°C. Esters are formed when alcohols are included. Anhydrous conditions are desirable to minimize the formation of by-products including acetaldehyde and carbon dioxide (see Acetaldehyde). 

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