Organopalladium reactions

Another useful feature of the organopalladium reaction is that it can produce fairly hindered olefins from ortho-substituted aromatic mercurials. For example, "2,4,6-triisopropylphenylpalladium chloride , prepared in situ, from the mercurial and lithium chloropalladate in acetonitrile solution, reacts with styrene to produce a 40% yield of fra s-2,4,6-triisopropylstilbene. This is about the same yield of product that is obtained with the unsubstituted "phenylpalladium chloride under the same conditions 24>. 

The numerous palladium-catalyzed organic reactions have a relatively small number of elementary steps. Oxidative Addition, Reductive Elimination, ligand coordination, and addition to coordinated ligands (either intramolecular or intermolecu-lar) are the most important classes of transformations in most palladium catalytic cycles. The exact nature of the species within the coordination sphere of palladium and the order in which the steps take place are responsible for the variety of the organic products produced. Four representative and important palladium-catalyzed reactions are briefly discussed here to illustrate the range of organopalladium reactions. 

S. Brase, J. Kobberling, and N. Griebenow, Organopalladium Reactions in Combinatorial Chemistry, in Handbook of Organopalladium Chemistry for Organic Synthesis , ed. E. Negishi, John WUey Sons, Hoboken, NJ, 2002, p. 3031. 

Braese, S., Kobberling, J., Griebenow, N. Organopalladium reactions in combinatorial chemistry. Handbook of Organopalladium Chemistry... 

Although ester groups do not normally participate in organopalladium reactions, o-halobenzoate esters react with internal alkynes in the presence of a palladium catalyst to produce good yields of isocoumarins (Eq. 36) [72,77,78]. 

It is indeed advisable not to consider any compounds to be inert to Pd and its complexes. Tertiary amines, such as EtjN, are often used mainly to neutralize some acids generated as by-products. However, amines can react with Pd complexes to undergo oxidation, as discussed in Sect, vni.3.2. So, unless the desired reaction is much faster than this oxidation reaction, there can be some undesirable consequences. Many solvents, snch as HOAc, are also reactive with Pd complexes. In some cases, such reactions have been shown to be essential to observing favorable results (Sect IV.4). Even a small amount of adventicious impurities, such as HjO, can significantly alter the courses of organopalladium reactions, as discussed in Sect. VI.4.3, even though many other organopalladium reactions can be satisfactorily carried out in water, where the molar ratio of water to substrate may exceed 1(X). 

Even without mechanistic information, one can begin to rationalize and, perhaps more importantly, predict various catalytic organopalladium reactions in consultation with Table 3 and Scheme 3. For example, the following four reactions shown in Scheme 5 are representative of the four most important types of Pd-catalyzed C—C bond formation processes discussed in detail in Parts III-VI. It is useful to note that only four patterns in Table 3, that is, (i) carbopalladation, (ii) reductive elimination, (iii) migratory insertion, and (iv) nucleophilic (or electrophilic) attack on ligands, can achieve C—C bond formation. This summary can also be appropriately modified for the formation of other types of bonds, such as C—H, C— M, C— X, and X— X bonds, where M is a metal and X is a heteroatom. 

The versatility of Pd is very well indicated by the contents of this Handbook listing nearly 150 authored sections spread over ten parts. This Handbook cannot and does not list all examples of the organopalladium reactions. However, efforts have been made to consider all conceivable Pd-catalyzed organic transformations and discuss all known ones, even though it was necessary to omit about ten topics for various unfortunate reasons. 

The results summarized under the headings 1 and 2 rather conclusively indicate that, under the conditions used, the reaction must proceed via hydropaUadation. For the other steps, a combination of oxidative addition and reductive elimination, as in the Chalk-Harrod mechanism, is plausible, but other possibilities involving metathetical processes may not be ruled out. It should be noted that the two reactions employed by Brookhart and co-workers " and Hayashi and co-workers are substantially different. It is therefore very likely that the mechanistic conclusions made in their studies are both fundamentally correct and that, as in many other reactions of organopalladium compounds, more than one mechanism operates for a given type or class of organopalladium reactions. 

X.3 ORGANOPALLADIUM REACTIONS IN COMBINATORIAL CHEMISTRY 3113 Reactions Involving 7T-Allyl Complexes... 

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