Palladium, cyclopalladated compounds

To a suspension of the cyclopalladated compound (12.95 g, 47 mmol) in acetone (300 mL) is added an excess of LiCl (6.77 g, 150 mmol). This mixture is heated with vigorous stirring until the precipitate has dissolved. It is likely that with an excess of LiCl the salt Li[PdC6H4CH2N(CH3)2Cl2] is formed, which is stable only in acetone in the absence of water. Addition of water to this solution affords immediately the chloro-bridged dimer. The yellow solution is then quickly filtered over a short column of Celite (3 cm) to retain the finely divided metallic palladium and the column washed with 50 mL of acetone. The solution thus obtained is poured into a beaker containing 400 mL of water affording a yellow precipitate. The more quickly this operation is done the better the yield of the reaction the overall time of this purification should not... 

These inserted compounds 7.23-7.25 showed unexpected thermal stability so that no reaction performed to recover the modified palladium-free ligand led to clean products. However, the stability of these compounds is very much dependent upon the nature of the other ligands on the Pd atom. Thus, changing the chloride for an iodide led to a dramatic decrease in the thermal stability of the cyclopalladated compounds [82-84]. In reactions of this latter type, the total or partial dealkylation of the NMe2 group occurs to produce compound 7.26 or compound 121, respectively, as shown in Eq. (7.24). In a related reaction, it was possible to detect the presence of Mel together with an amount of CH4 [82]. 

With respect to medical applications of cyclopalladation compounds, Ryabov [70] reported in 2008 that the first systematic study on the cytotoxicity of cyclometalated palladium compounds was undertaken by Higgins ni et al. [71], The compounds were saeened for cytotoxicity against a panel of seven human tumor cell lines, as shown in Table 9.1. 

R.F. Heck, Best Synthetic Methods - Palladium Reagents in Organic Synthesis, Academic Press, London and Orlando FL, 1985. A.D. Ryabov, The Application of Cyclopalladated Compounds in Synthesis, Russ.Chem. Rev., 1985, 153. 

Pfeffer and coworkers8l-83 have shown that heterobimetallic complexes containing M-M bonds can be synthesized through the reactions of carbonylmetallate anions with cyclopalladated compounds. Reaction between the palladium(II) complex (Figure 5.5) and Na[Mo(CO)3Cp] takes place only when hexane is added to a mixture of the starting materials in THF. 

Ghedini reported a number of mononuclear cyclopalladated 2-phenylpy-rimidine complexes, some of them, 17 and 18, showing mesomorphic properties [26]. These compounds were obtained by bridge splitting reactions from the dinuclear (/ -chloropyrimidine)palladium(II) complexes with various acetylacetone and dinitrogen ligands. 

These alkenylation products are easily utilized for the formation of heterocyclic compounds by cyclization reactions. For example, ethyl A -methyl-lV-(3,4-methylenedioxy)benzylglycinate is cyclopalladated regiospecifically at C(6) when treated with Li2PdCl4. The product, the di-p-chloro-bis(AOV-dialkylbenzylamine-6-C,iV)-dipalladium(II) complex 7.19, undergoes a substitution reaction via the insertion of methyl vinyl ketone between the palladium metal and the phenyl carbon atom. The resultant p-aryl-a,p-unsaturated ketone 7.20 is cyclized using anhydrous potassium carbonate in ethanol to the corresponding ethyl iV-methyl-1,2,3,4-tetrahydroisoquinolinium-3-carboxylate 7.21, as shown in Eq. (7.19) [76, 77]. 

A chloro-bridged cyclopalladated pyridine compound is also carbonylated by the reaction of carbon monoxide with bubbling through a reaction mixture at room temperature in the presence of NEts as a proton scavenger. Metalhc palladium is separated out, while ethyl ester 7.62 is recovered in a 73 % yield, as shown in Eq. (7.41) [94]. 

Cyclometalations proceed as shown in eqs. (20.35)-(20.39). With palladium compounds, these reactions are called cyclopalladation or orthopalladation. As the palladium bonded to an aromatic ring is very reactive, alkenes, alkynes, CO and halogen are easily replaced. For example, as shown in eq. (20.61), ortho-aryl derivatives are seleetively prepared in high yield [212]. 

Cyclopalladation products react with alkynes to be inserted into the palladium-carbon bond, followed by reductive elimination of Pd(0), which leads to the formation of a C-N bond. Then the heterocyclic compound is yielded as shown in eq. (20.62) [195,213]. 

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