Palladium Intermediates in Solution

Mass spectrometry with electrospray ionization (ESI-MS) [3] has become a useful alternative for the determination of the reactive intermediates given that it enables the simple direct detection of the components of the reaction mixture and, at the same time, allows starting compounds, intermediates and final products to be monitored. The technique has recently been applied to the determination of mechanisms in highly diverse reactions [4]. The main function of the ESI process is to transfer analyte species which are normally ionized in the condensed phase into the gas phase as isolated entities. The species must be charged in order to allow the detection of intermediates and to have a sufficiently long lifetime. For samples which already contain ions, no further ionization is needed. However, the common sample 

1) Dedicated to the memory of our friend Prof. Mardal Moreno-Manas. 

In this chapter we will concentrate on the mechanistic studies that have been conducted to date on palladium-catalyzed reactions, including not only those ESI-MS studies which are highly specific and complete but also ones that merely touch on this technique. In these mechanistic studies it is crucial to take into account the need to analyze the detected species carefully by ESI-MS to make absolutely certain that the ones which prevail in the solution are in fact intermediates on the reaction path. 

A series of steps must be taken to ensure that the mechanistic study is methodologically correct, (i) In a first set of experiments the individual behavior of each of the reactants, final products, catalysts and additives needs to be studied by ESI-MS. 

One of the advantages of these mechanistic studies involving palladium species is that the peaks in the mass spectra due to intermediates containing this metal are immediately identified by their characteristic isotope distribution [isotope distribution of palladium Pd (1.02%), Pd (11.14%), Pd (22.33%), Pd (27.33%), 

---

Isomerization and Inversion, cis trans isomerization of cyano-complexes [Pd(CN)2-(PR3)2l, where, interestingly and unusually, the rraw-isomer is thermodynamically the more stable, is thought to take place by an associative mechanism. Though it did not prove possible to detect a five-co-ordinate intermediate in solution, it was felt that the cyanide ligands would stabilize such a transient intermediate or transition state. An associative mechanism, involving solvent participation, is also proposed for cis trans isomerization of isocyanate-phosphine-palladium(ii) complexes in several solvents. ... 

A synthetically useful virtue of enol triflates is that they are amenable to palladium-catalyzed carbon-carbon bond-forming reactions under mild conditions. When a solution of enol triflate 21 and tetrakis(triphenylphosphine)palladium(o) in benzene is treated with a mixture of terminal alkyne 17, n-propylamine, and cuprous iodide,17 intermediate 22 is formed in 76-84% yield. Although a partial hydrogenation of the alkyne in 22 could conceivably secure the formation of the cis C1-C2 olefin, a chemoselective hydrobora-tion/protonation sequence was found to be a much more reliable and suitable alternative. Thus, sequential hydroboration of the alkyne 22 with dicyclohexylborane, protonolysis, oxidative workup, and hydrolysis of the oxabicyclo[2.2.2]octyl ester protecting group gives dienic carboxylic acid 15 in a yield of 86% from 22. 

Substantially more work has been done on reactions of square-planar nickel, palladium, and platinum alkyl and aryl complexes with isocyanides. A communication by Otsuka et al. (108) described the initial work in this area. These workers carried out oxidative addition reactions with Ni(CNBu )4 and with [Pd(CNBu )2] (. In a reaction of the latter compound with methyl iodide the complex, Pd(CNBu )2(CH3)I, stable as a solid but unstable in solution, was obtained. This complex when dissolved in toluene proceeds through an intermediate believed to be dimeric, which then reacts with an additional ligand L (CNBu or PPh3) to give PdL(CNBu )- C(CH3)=NBu I [Eq. (7)]. 

In 2003, Sigman et al. reported the use of a chiral carbene ligand in conjunction with the chiral base (-)-sparteine in the palladium(II) catalyzed oxidative kinetic resolution of secondary alcohols [26]. The dimeric palladium complexes 51a-b used in this reaction were obtained in two steps from N,N -diaryl chiral imidazolinium salts derived from (S, S) or (R,R) diphenylethane diamine (Scheme 28). The carbenes were generated by deprotonation of the salts with t-BuOK in THF and reacted in situ with dimeric palladium al-lyl chloride. The intermediate NHC - Pd(allyl)Cl complexes 52 are air-stable and were isolated in 92-95% yield after silica gel chromatography. Two diaster corners in a ratio of approximately 2 1 are present in solution (CDCI3). 

If the unsaturated hydrocarbon is a diene, both double bonds may coordinate to palladium ). (Diene)palladium(II) complexes have been isolated and characterized. For example, 2 and 3 are stable complexes in which both double bonds are coordinated to the metal10. Conjugated dienes constitute a special case and although /j4-diene complexes, e.g. 4, are postulated as intermediates, they have not yet been isolated. The butadiene complex 4 is in equilibrium with the zr-allyl complex 5 in solution, and attempts to isolate the diene complex from this mixture lead to formation of a yellow crystalline complex 511. 

Michaelis, M. and Henglein, A., Reduction of palladium (II) in aqueous solution stabilization and reactions of an intermediate cluster and palladium colloid formation, J. Phys. Chem., 96, 4719, 1992. 

---