Palladium catalysis aromatic

The three-component synthesis of benzo and naphthofuran-2(3H)-ones from the corresponding aromatic alcohol (phenols or naphthols) with aldehydes and CO (5 bar) can be performed under palladium catalysis (Scheme 16) [59,60]. The mechanism involves consecutive Friedel-Crafts-type aromatic alkylation and carbonylation of an intermediate benzylpalla-dium species. The presence of acidic cocatalysts such as TFA and electron-donating substituents in ortho-position (no reaction with benzyl alcohol ) proved beneficial for both reaction steps. 

Ellman used silyl chemistry for the direct linkage of aromatics onto the solid support by converting an aryl bromide to aryl lithium and reacting this with a silyl resin.90 It is the production of the silyl resin that is of interest in the context of this review, since an in situ Suzuki coupling was used to link the allyl silane to bromomethyl polystyrene resin (Scheme 40). 9-BBN is used to carry out the regioselective hydroboration, and this is linked to the resin with palladium catalysis in the usual way. After brief exposure of this... 

It is reported that the palladium-catalysed intramolecular aromatization of 1,1 -dichloro-9/T-fluoren-9-yIidene (15) may lead to the formation of fullerene fragments.89 The amiulation reaction, under palladium catalysis, between iodoanflines and ketones may yield indole derivatives.90 There have also been studies of the palladium-catalysed carbonylation of o-iodophenols with allenes which may lead to l-benzopyran-4-one derivatives,91 of the intramolecular coupling of phenols with aryl halides,92 and of the intramolecular Heck aiylation of cyclic enamides.93... 

As described in Section III.1.4.1.1, the catalytic direct arylation reactions of aromatic compounds occurs effectively via C-H bond cleavage when the substrates are appropriately functionalized. On the other hand, various five-membered heteroaromatic compounds involving one or two heteroatoms, even without a functional group, are known to undergo arylation, usually at their 2- and/or 5-posi-tion(s), on treatment with aryl halides under the action of palladium catalysis. The coupling has recently been developed significantly [1, 2]. Representative examples with some mechanistic discussion are summarized in this section. 

As in the Skraup quinoline synthesis, loss of two hydrogen atoms is necessary to reach the fully aromatic system. However, this is usually accomplished in a separate step, utilising palladium catalysis to give generalised isoquinoline 6.14. This is known as the Bischler-Napieralski synthesis. The mechanism probably involves conversion of amide 6.12 to protonated imidoyl chloride 6.15 followed by electrophilic aromatic substitution to give 6.13. (For a similar activation of an amide to an electrophilic species see the Vilsmeier reaction, Chapter 2.)... 

While the major use for palladium catalysis is to make carbon-carbon bonds, which are difficult to make using conventional reactions, the success of this approach has recently led to its application to forming carbon-heteroatom bonds as well. The Overall result is a nucleophilic substitution at a vinylic or aromatic centre, which would not normally be possible. A range of aromatic amines can be prepared direcdy from the corresponding bromides, iodides, or triflates and the required amine in the presence of palladium(O) and a strong alkoxide base. Similarly, lithium thiolates couple with vinylic triflates to give vinyl sulfides provided lithium chloride is present. 

The direct coupling of aromatic systems has been achieved in the generation of 2-arylpyridines. These frameworks have been of importance in material and medicinal chemistry. The Pd-catalyzed Ullmann reaction afforded 2-nitrophenylpyridine derivatives that served as precursors to 2-substituted-phenylpyridines, which are found to have antiarrhythmic activity [152], To this end, 3-iodopyridine 152 could be directly coupled to 429 by palladium-catalysis to afford 430. 

The reaction usually requires palladium catalysis. In the case of aromatic tosylates [23] or arylchlorides, Ni-catalysts [20, 21] or Pd-imidazole-2-ylidene complexes had to be employed ]33]. The latter catalyst is generated in situ from 1,3-bisaryl or 1,3-bisalkyl imidazolidinium chloride ]34, 35] and a base, such as CS2CO3 or KOtBu ]36]. 

The most common means of activating aromatic C-H bonds via palladium catalysis is by electrophilic C-H activation. This proceeds more like a Freidel-Craft type metahation mechanism, followed by rearomatization to form versatile aryl-metal intermediates (Scheme 5) [19]. It can occur with electrophilic palladium(II) catalysts such as Pd(OAc)2, PdCl2, Pd(TFA)2 (Scheme 5a) or on electrophilic aryl-pahadium(II) complexes, that result from oxidative addition of palladium(O) into an aryl halide (Scheme 5b). The resultant aryl-palladium(H) complexes are analogous to those observed in conventional cross-coupling reactions and as such are versatile intermediates in the formation of new C-C bonds. 

With palladium catalysis, refluxing in nitrobenzene or xylene dehydrogenates 3-substituted 5,6,7,8-tetrahydropyrido[4,3-rf]pyrimidin-4(3//)-ones to yield the corresponding aromatic compounds. Thus, the 3-phenyl compound is dehydrogenated by heating in nitrobenzene with palladium on carbon at 125 130°C for 17 hours.509... 

Biaryl structures are found in a wide range of important compounds, including natural products and organic functional materials [8,80,81]. One of the most common and useful methods for preparing biaryls is the palladium-catalyzed coupling of aryl halides with arylmetals (Scheme 1, mechanism A). On the other hand, aryl halides have been known to couple directly with aromatic compounds as formal nucleophiles under palladium catalysis. While the intramolecular cases are particularly effective, certain functionalized aromatic compounds such as phenols and aromatic carbonyl compounds, as well as... 

Heterogeneous hydrogenation, especially with palladium catalysis, is not normally selective and, in addition to hydrogenation of alkenes, hydrogenolysis of benzyl ethers occurs readily (although aromatic heterocycles are not normally reduced under these conditions). Therefore in this case the product is as shown below ... 

We have already seen that p-bromophenol can be joined to an amine with palladium catalysis, so it should be easy to join it to piperazine. However, there is a potential problem of selectivity we want to add this benzene ring just once, and the way to do this is to protect one nitrogen atom by reductive amination with benzaldehyde. The remaining NH group can then be coupled to the aromatic ring and the benzyl group removed by hydrogenation. 

Nucleophilic aromatic substitution and palladium catalysis compared... 

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