Palladium-mediated reactions

The palladium-promoted conversion of 1,3-dienes to pyrroles proceeds via 4-acetoxy-2-alkenylpalladium complexes (Scheme 50g) (81CC59), and a similar pathway may be involved in the palladium mediated reaction of but-2-ene-l,4-diol with primary amines to give A-substituted pyrroles (74CC931). 

In summary, palladium-mediated reactions, especially cross-coupling reactions have found many applications in quinoline synthesis. It is noteworthy that due to the a and S activation for the C(2) and C(4) positions, even 2-chloro- and 4-chloro-quinolines are viable substrates for palladium-catalyzed reactions under standard conditions. With the advent of the palladium chemistry and more commercially available organometallic substrates, more palladium-mediated quinoline syntheses are to be added to the repertoire of quinoline chemistry. 

Palladium chemistry of heterocycles has its idiosyncrasies stemming from their different structural properties from the corresponding carbocyclic aryl compounds. Even activated chloroheterocycles are sufficiently reactive to undergo Pd-catalyzed reactions. As a consequence of a and y activation of heteroaryl halides, Pd-catalyzed chemistry may take place regioselectively at the activated positions, a phenomenon rarely seen in carbocyclic aryl halides. In addition, another salient peculiarity in palladium chemistry of heterocycles is the so-called heteroaryl Heck reaction . For instance, while intermolecular palladium-catalyzed arylations of carbocyclic arenes are rare, palladium-catalyzed arylations of azoles and many other heterocycles readily take place. Therefore, the principal aim of this book is to highlight important palladium-mediated reactions of heterocycles with emphasis on the unique characteristics of individual heterocycles. 

Less than two years after Chan and I disclosed the synthesis of 72 and 73, a more practical synthesis of 72 based on palladium-mediated reactions was reported by Armin de Meijere. I was deeply impressed by the highly efficient way Armin and his co-worker, Oliver Reiser, were preparing 72 as well as its derivatives. Immediately, I realized that it was impractical to compete with them. I therefore quit the dibenzo[2.2]paracyclophane field, with the strong conviction that many other unknown theoretically interesting molecules were still waiting for our pursuit. 

It has been found that 1,2,4-oxadiazoles 255 can be obtained from amidoximes 254 and aryl iodides by the palladium-mediated reaction in the presence of carbon monooxide. This reaction was applicable to both electron rich and deficient aryl iodides (equation 110) °. Amidoximes in the system Arl+ Ph X /CO/PdCH/KiCOs/NMP/tolnene also afforded 5 -aryl-1,2,4-oxadiazoles. ... 

Both pyrimidine and quinazoline derivatives have been investigated as ligands for palladium-mediated reactions. Examples of ligands prepared include the phosphine-free bipyrimidine 1181, which gave the isolable palladium dichloride catalyst 1182 <2001JOM(634)39>, and the chiral oxazolinyl-quinazoline BINAP analogs 1183 and 1184 <20060L5109>. 

Palladium chemistry has rapidly become an indispensable tool for synthetic organic chemists. Palladium-catalyzed coupling is now the method of choice for the synthesis of a wide range of biaryls and heterobiaryls. The number of applications of palladium chemistry to the syntheses of heterocycles has grown exponentially. In this book important palladium-mediated reactions involving heterocycles are highlighted with emphasis on the unique characteristics of individual heterocycles. 

Benzofurans and dihydrobenzofurans have been prepared on polymeric supports by the palladium-mediated reaction of 2-iodophenols with dienes or alkynes (Entries 1 and 2, Table 15.9). This reaction is closely related to the synthesis of indoles from 2-iodoanilines, and probably proceeds via an intermediate palladacycle (Figure 15.3). Benzofuran and isobenzofuran derivatives have also been prepared on cross-linked polystyrene by intramolecular addition of aryl radicals to C=C double bonds and by intramolecular Heck reaction. 

The synthetic strategies used for the preparation of pyrans on insoluble supports have mainly been hetero-Diels-Alder reactions of enones with enol ethers and ringclosing olefin metathesis (Table 15.33). Benzopyrans have been prepared by hetero-Diels-Alder reactions of polystyrene-bound o-quinodimethanes with aldehydes. The required quinodimethanes were generated by thermolysis of benzocyclobutanes, which were prepared in solution [308]. Other solid-phase procedures for the preparation of benzopyrans are the palladium-mediated reaction of support-bound 2-iodo-phenols with 1,4-dienes (Entry 5, Table 15.33) and the intramolecular Knoevenagel... 

A functionalized mercury(II) compound like ethyl (acetoxymercurio)acetate (136) allows an easy approach to prostaglandin endoperoxide analogs (equation 52).204 Several organomercury(II) compounds, RHgCl (R = Me, aryl, benzylic), are able to add to 1,3-dienes in the presence of a stoichiometric amount of a palladium(II) salt and affonl ir-allylpalladium compounds of type (137) in variable yields (equation 53).20S A related intramolecular carbomercuration has been reported by Snider.206 It allows a stercospe-cific approach to the chloromercury compound (138 equation 54). Similar palladium-mediated reactions... 

Palladium-mediated Reaction of Vinylic Halides with Alkenes... 

What kind of palladium-mediated reactions are known ... 

An interesting reaction of disilane is the transition metal-catalyzed insertion of unsaturated hydrocarbons. The palladium-mediated reaction of cyclotrisilane 26 with phenylacetylene to afford the seven-membered carbosilane 51 (Equation 3) indicates that this general reaction scheme is also applicable to strained cyclic trisilanes <20040M490>. 

B. Metal-Catalyzed Reactions Palladium-Mediated Reactions... 

Cheng, J C Y, Daves, G D Jr, C-glycosides from palladium-mediated reactions of pyranoid glycals. Stereochemistry of formation of intermediate organopalladium adducts and factors affecting their stability and decomposition, J. Org. Chem., 52, 3083-3090, 1987. 

The copper and palladium transition metal catalysts noted in Table 18 proved to be superior to nickel, ruthenium and rhodium catalysts. The nature of the reacting species has not been unequivocally defined, but the following experimental observations may provide some insight (i) tetrahydrofuran solvent is essential for the palladium-mediated reactions, since complex reaction mixtures (presumably containing carbinols) were observed when the reactions were performed in either benzene or methylene chloride (ii) the reaction is truly catalytic with respect to palladium (2 mmol alkylaluminum, 0.05 mmol of Pd(PPh3)4), whereas the copper catdyst is stoichiometric and (iii) in the case where a direct comparison may be made (entries 1-8, Table 18), the copper-based system is superior to palladium catalysis with regard to overall yield. 

On the other hand, palladium-catalyzed reaction of p-benzoquinone with cyclic organosilanes having Si-Si bonds provides organosilicon polymers 82 (Eq.41) [74]. Interestingly, dodecamethylcyclohexasilane, known as one of the least reactive oligosilanes in palladium-mediated reactions, is usable for the co-polym-erization. 

Chapter 3 by Jie Jack Li presents a collection of very interesting total syntheses of naturally occurring indole alkaloids where palladium chemistry plays a central role in the syntheses. Five different types of palladium-mediated reactions are treated (I) oxidative cyclization reactions promoted by palladium (II) species (2) transmetallation reactions with organoboranes, organoslannanes, and organozinc reagents (3) inter- and intramolecular Heck reactions (4) reactions with it-allylpalladium as the intermediate and (5) reactions using C-N bond formation as the key step for the synthesis. 

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