Palladium arylation

The rate equation for the reaction scheme in Figure 13.17 shows a zero order dependence in aryl iodide and base, a first order in alkene, and a square root order in the palladium concentration. We can conclude from this that either the complexation of acrylate to palladium or its insertion in the palladium-aryl bond is rate-determining. 

The use of cyclic alkenes as substrates or the preparation of cyclic structures in the Heck reaction allows an asymmetric variation of the Heck reaction. An example of an intermolecular process is the addition of arenes to 1,2-dihydro furan using BINAP as the ligand, reported by Hayashi [23], Since the addition of palladium-aryl occurs in a syn fashion to a cyclic compound, the 13-hydride elimination cannot take place at the carbon that carries the phenyl group just added (carbon 1), and therefore it takes place at the carbon atom at the other side of palladium (carbon 3). The normal Heck products would not be chiral because an alkene is formed at the position where the aryl group is added. A side-reaction that occurs is the isomerisation of the alkene. Figure 13.20 illustrates this, omitting catalyst details and isomerisation products. 

Ini Hally, oxidaiive addition of the 2-chloroquinolme 9 to a Pd° species leads to complex 30, which contains Pd11 Carbonylation then occurs through CO insertion into the palladium-aryl bond, giving intermediate 31. finally, methanolysis releases methyl ester 10, and the Pd° species is regenerated. 

In the original process using tin amides, transmetallation formed the amido intermediate. However, this synthetic method is outdated and the transfer of amides from tin to palladium will not be discussed. In the tin-free processes, reaction of palladium aryl halide complexes with amine and base generates palladium amide intermediates. One pathway for generation of the amido complex from amine and base would be reaction of the metal complex with the small concentration of amide that is present in the reaction mixtures. This pathway seems unlikely considering the two directly observed alternative pathways discussed below and the absence of benzyne and radical nucleophilic aromatic substitution products that would be generated from the reaction of alkali amide with aryl halides. 

Carbon monoxide insertions into palladium-alkyl or palladium-aryl bonds were extensively studied in connection with the palladium-catalyzed CO-olefin copolymerization process . 

The mechanism of palladium/aryl halide amination is very closely related to that of cross coupling, with displacement of the halide on palladium (or copper or nickel) by an amine or A-anion instead of the trans-metallation step. In the case of Cu and Ni catalysis, it may proceed through M(0)-M(11) or M(l)-M(lll) cycles. 

With palladium, high yields of 7i-allyl complexes may also be obtained from palladium aryls and palladium alkyls lacking p hydrogens . Complexes LVIII are prepared via the... 

According to the proposed reaction mechanism (Scheme 44), carbopalla-dation of benzyne with the 7i-allyl palladium complex gives intermediate 157. Insertion of CO in the palladium-aryl bond then leads to the acyl palladium complex 158, which undergoes intramolecular cyclization and subsequent P-hydride elimination, affording indanone 156 [78]. 

The oxidative addition of an aryl iodide to a zerovalent complex such as [Pd(PPh3)4] gives tra s-[Pd(Ar)I(PPh3)2] having a palladium-aryl and a palladium-iodide bond indeed, this is one of the oldest examples of oxidative addition of aryl iodide to Pd(0) complex (Eq. 1.1) [10]. 

A complex with a palladium-aryl bond [Pd(I)(C6H3Me2-3,5)(bipy)], prepared from [Pd(dba)2l, 2-2 -bipyridine, and 3,5-Me2C6H3l, enters the insertion reaction with dimethylacetylene dicarboxylate and silver tetrafluoroborate in acetone to yield 74 (OOOM2125). In the absence of silver tetrafluoroborate, the insertion reaction leads to 75. It reacts with silver tetrafluoroborate to yield cationic 76 (010M1087). If dimethylacetylene dicarboxylate is taken in excess, then in the presence of silver tetrafluoroborate, 77 is the product. [Pd(I)(C6H3Me2-3,5)(bipy)] also reacts with phenylallene and silver tetrafluoroborate in acetone, and the reaction is accompanied by the insertion of the C = C bond into the palladium-aryl bond to yield palladium allyl 78. 

Ort/io-metallated palladium complexes of azo and hydrazobenzene catalyze the reduction by H2 of nitroaromatics, alkenes, alkynes, and aromatic carbonyl compounds. A palladium-aryl or bond in the precursor complex is a requirement for catalytic activity. The ligands are themselves susceptible to reduction. The kinetics of the reaction under 1 atm H2 have been measured. Palladium(O) complexes catalyze the hydrostannolysis of allyl and allyloxy carbonyl groups. The reaction can be applied to the selective protection-deprotection of aminoacid derivatives see equation (9). Alkenyl cyclopropanes carrying electron-withdrawing substituents are selectively hydrogenolyzed by Pd(0)/PBu3 catalysts... 

On the other hand, true ligand acceleration (type 3 processes) shows preference for solvents of low polarity and lower Lewis basicity (toluene, dioxane and THF) with soluble tertiary amines as bases. In this respect, these Mizoroki-Heck reactions resemble cross-coupling processes, which also display strong preference for these solvents. Reactions in nonpolar solvents (toluene or xylene) have been known since Heck s seminal articles [8]. The halide remains a crucial subject of concern in reactions catalysed by phosphine complexes of palladium, aryl iodides prefer triarylphosphines and polar solvents, whereas reactions of aryl bromides and chlorides indeed prefer electron-rich trialkylphosphines and nonpolar solvents [63-65]. 

The results indicate that the rate- and regio-determining step involves concerted metalation-deprotonation, as shown in (23), to give an aryl palladium intermediate. This is followed by substitution of the pyridine ligand, L, by the alkene and insertion of the alkene double bond into the palladium—aryl bond. The absence of ortho-substituted product results from steric repulsion between the ring substituent,... 

Several approaches have been used to prepare transition-metal-thiolate complexes. The most common synthetic route involves the metathesis reaction of a metal halide with an alkali metal thiolate salt. For instance, [(DPPE)Pd(Ar)(S-t-Bu)] was obtained by treatment of the (DPPE) palladium aryl iodide complex with sodium fprf-butyl thiolate (Equaticm 4.106). Additionally, these compoimds have been formed by proton exchange reactions of thiols with M-C (Equation 4.107), ° M-W and M-O, bonds (Equation 4.108). Finally, the oxidative addition of RSH, or alkyl and aryl disulfides - is a useful way... 

Brookhart on the insertion of a single ethylene into a branched alkyl complex of nickel and an example of the 2,1-insertion of vinylacetate into the palladium-methyl complex to form a stable chelated product. Equation 9.65 shows the insertion of a vinylarene into a palladium-aryl complex that is an intermediate in the vinylation of aryl halides known as the Heck reactioa... 

Careful mechanistic studies on the carbonylation process have been reported by Yamamoto, including studies with isolated model compounds. - These studies have revealed several reaction pathways, and the particular pathway depends on whether the electrophile is an aryl or benzyl halide and whether the nucleophile is an amine or an alkoxide. The existing experimental data suggest that the latter pathway b in Scheme 17.29 involving insertion of CO into the palladium-aryl bond to form a benzoylpalladium halide intermediate occurs. These complexes have been isolated with PMe and PPhj as ligand and have been shown to form the ester product upon reaction with an alcohol and amine base and to form the amide products upon reaction with amine alone. 

Examples of the formylation of aryl halides with synthesis gas catalyzed by palladium complexes are summarized in Equation 19.90. These reactions relied upon the development of ligands with particular steric and electronic properties. The dia-damantyl-n-butyl phosphine shown in the equation, in combination with palladium acetate, leads to the formation of aromatic aldehydes in high yields from electron-rich and electron-poor aryl bromides. Reactions of nitroarenes and 2-bromopyridine provided the aldehydes in low yield, but other examples occurred in satisfactor) yield with only 0.1-0.75 mol % catalyst. The identity of the base is important in this process, and TMEDA was the most effective base. The mechanism of this process was not proposed in the initial work, but is likely to occur by oxidative addition of the aryl halide, insertion of the carbon monoxide into the palladium-aryl bond, and a combination of hydrogenolysis of the acyl intermediate and elimination of hydrogen halide to regenerate palladium(O). The base would then be involved in the hydrogenol5 sis and consumption of hydrogen halide. 

One of the most versatile and widely employed methods for the construction of aryl C—N bonds is the palladium-catalyzed cross coupling of amines with aryl halides and related electrophiles [4]. These reactions are believed to occur as shown in Scheme 1.1, with the coupling initiated by oxidative addition of the aryl halide to a Pd° complex. The resulting intermediate 1 is converted to a palladium(aryl)(amido) complex 2 through reaction with the amine substrate in the presence of base. Finally,... 

The analogous methoxy carbene complexes could not be isolated by following this carbene transfer route, and instead products of carbene insertion into the palladium-aryl bond 54 are observed, for example. Equation (20). These reactions are directly analogous with those observed for alkyl- and arylpalladium heterocyclic carbene complexes, in which both reductive elimination and carbene insertion reactions have been observed (Section 8.04.2.3.4). 

A digital functional approach has been employed to investigate important steps in the Heck reaction catalyzed by a bis(carbene)Pd complex and one in which the Pd is coordinated by a bidentate carbene-phosphine ligand. The crucial steps of olefin insertion into the palladium-aryl bond and / -hydride elimination were investigated. For the bis(carbene)Pd catalyst, a mechanism was proposed, which proceeds via halide abstraction, to give a cationic species, prior to olefin coordination and insertion. The total insertion/elimination process was found to be exothermic (—8.9 kcal moP ). For the carbene-phosphine ligated system, the vacant site for olefin coordination was provided by phosphine dissociation. The energetics for the total insertion/elimination process was very similar to that of the bis-carbene system. 

Coupling of Aryl Halides and Nucleophiles. Couplings of aryl halides and other nucleophiles have been successfully carried out using combinations of TTBP and palladium. Aryl bromides were coupled with amines at room temperature using TTBP/Pd2(dba)3, while aryl chlorides were aminated at elevated temperatures (50-100 °C, eq A) Other nucleophiles, such as enolates, can be coupled with aryl bromides and chlorides under mild conditions using TTBP in combination with palladium complexes (eq Although conparison stud-... 

Carbene Insertion into the Palladium-Aryl Bond... 

Using a similar concept, Wolfe and Rossi developed a novel palladium-catalyzed stereoselective synthesis of tetrahydrofurans from y-hydroxy alkenes and aryl bromides [27] (Scheme 6.17). After a series of deuterium labeling experiments, the authors suggested that the predominant mechanistic pathway for tetrahydrofiiran formation probably involves a rare syn insertion of an alkene into the Pd-O bond of an intermediate palladium aryl alkoxide [28]. Later, the same group reported similar intramolecular [29] and intermolecular [30] cyclizations to synthesize a series of tetrahydrofurans. 

Experimental evidence for insertion of alkenes into the metal-nitrogen bond was reported recently in the studies of aminopalladation reactions [41,42]. Intramolecular insertion reaction was confirmed to be a yn-addition process and was monitored by NMR spectroscopy of the well-defined palladium(aryl)(amido) complexes (Scheme 11) [41, 43]. The reaction proceeded as insertion into Pd-N bond with complete chemoselectivity and the alternative route of alkene insertion into the Pd-C bond was not observed. The activation enthalpy determined for the insertion step A// = 24.8 zb 0.6 kcal/mol was comparable with the values reported for other insertion reactions, and small activation entropy = 4.6 zb 1.8 eu is consistent with intramolecular transformation [41, 43]. The final product of the reaction was formed after C-C reductive elimination, which is known to be rather fast step if at least one aryl group is involved [44, 45]. The mechanistic study of the alkene insertion into the Pd-N bond has also pointed out on possible reversible nature of such process [46]. 

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