Palladium carbonylative coupling

Another compound 9 with three heterocyclic rings linearly fused (5 5 5) with two heteroatoms has been prepared from 1,1 -carbonyl diindole 297 <2001T5199>. Palladium-mediated coupling of the 2- and 2 -positions of 297 afforded the 1,1 -carbonyl-2,2 -biindolyl 9. 1,1 -Carbonyl diindole 297 was in turn obtained in 41% yield from 1,1 -carbonyldiimidazole 296 by reaction with indole in DMSO at 125 °C. The palladium-catalyzed coupling step afforded the desired product 9 in low yield and required a stoichiometric amount of palladium acetate. Therefore, it was felt prohibitively expensive. Addition of various co-oxidants (Ac20, Mn02, and Cu(OAc)2, etc) to make the reaction catalytic in palladium did not result in any improvement of the yield of 18 (Scheme 53). 

Palladium(0)-catalyzed coupling reactions - i. e. the Heck and Sonogashira reactions, the carbonylative coupling reactions, the Suzuki and Stille cross-coupling reactions, and allylic substitutions (Fig. 11.1) - have enabled the formation of many kinds of carbon-carbon attachments that were previously very difficult to make. These reactions are usually robust and occur in the presence of a wide variety of functional groups. The reactions are, furthermore, autocatalytic (i.e. the substrate regenerates the required oxidation state of the palladium) and a vast number of different ligands can be used to fine-tune the reactivity and selectivity of the reactions. 

The Fukuyama indole synthesis involving radical cyclization of 2-alkenylisocyanides was extended by the author to allow preparation of2,3-disubstituted derivatives <00S429>. In this process, radical cyclization of 2-isocyanocinnamate (119) yields the 2-stannylindole 120, which upon treatment with iodine is converted into the 2-iodoindole 121. These N-unprotected 2-iodoindoles can then undergo a variety of palladium-catalyzed coupling reactions such as reaction with terminal acetylenes, terminal olefins, carbonylation and Suzuki coupling with phenyl borate to furnish the corresponding 2,3-disubstituted indoles. 

Muller and co-workers reported the three-component one-pot synthesis of various pyrimidines through the in situ generation of unsaturated carbonyl compounds. The palladium catalyzed coupling of aryl halides bearing electron withdrawing substituents 7 with propargyl alcohols 8 produced unsaturated carbonyl compounds 9 after isomerization, which condensed with amidines 10 to form triaryl pyrimidines 11 . 

The extraordinary power of the Ishikura palladium-catalyzed couplings of indolylborates is revealed by the several examples shown below [148,152,154,155]. The carbonylation version is discussed in Section 3.6. The formation of allenylindoles 139 vis-d-vis alkynylindoles 141 apparently depends on the equilibrium between an allenylpalladium complex and a propargylpalladium complex, and SN2-like attack on the latter by 136 to give 141 is favored by the Ph3P-ligated Pd complex. 

An acyl-palladium complex might undergo a series of follow up reactions. Subsequent transmetalation and reductive elimination lead to the formation of a carbonyl compound. This process is also coined carbonylative coupling, referring to the cross-coupling reaction, which would take place in the absence of carbon monoxide under similar conditions (for more details see Chapter 2.4.). 

Carbon monoxide, a common ligand in organometallic chemistry, is known to insert into palladium-carbon bonds readily. This feature of the metal is frequently utilized when palladium catalyzed reactions are run in the presence of CO. The products of such reactions, also known as carbonylative couplings, incorporate a carbonyl group between the coupling partners. 

Palladium-catalysed coupling also proceeded readily, carbonylative coupling in the presence of alcohols affording some particularly useful C-3 building blocks (Sect. 4.6) (Eq. 71) [224]. A metal-free method for generation of the trifluoroacetimidoyl carbanion has also been reported involving silic-ate formation and trapping [225]. 

The palladium-catalyzed coupling of homoallylzinc halides can also be used with /J-bromo-a./l-unsaturatcd carbonyl derivatives (equation 111).11... 

Bromo-3-[2-(t-butoxy carb onylamino)- 2-(ethoxy -carbonyl)ethenyl]-l-(4-methylphenylsulfonyl) B Arvlation by palladium-catalysed coupling 2-Methylbut-3-en-2-ol, Pd(PPh3)2Cl2, Ag2C03, Et3N 83 [3]... 

Palladium-catalysed coupling reactions under carbon monoxide have been extensively used in traditional medicinal chemistry72. Despite this, these crucial transformations have hardly been employed in combinatorial chemistry. These shortcomings have recently been recognised and a series of microwave-heated carbonylative transformations with solid or liquid CO-sources have been reported. 

Catalytic formation of carbon-carbon bonds is a powerful tool for construction of complex molecular architectures, and has been developed extensively for applications in organic synthesis. Three main classes of carbon-carbon bond forming reactions have been studied in sc C02 carbonylation (with particular attention paid to the hydroformylation of a-olefins), palladium-catalyzed coupling reactions involving aromatic halides, and olefin metathesis. 

Alkynyl(phenyl)iodonium salts can be effectively used in palladium(O) or copper(I) catalyzed coupling or carbonylative coupling reactions with various organozirconium complexes (Scheme 57) [117-119]. 

The application of organozinc iodides prepared in THF is illustrated in Protocols 4 and 5, which describe the palladium catalysed cross-coupling of a serine-derived organozinc iodide with a vinyl iodide, and the palladium catalysed carbonylative cross-coupling of another serine-derived organozinc iodide with a functionalized aromatic iodide. In the reaction with the vinyl iodide, it is important to transfer the solution of the organozinc iodide from the residual zinc, since this can react unproductively with the electrophile. In the case of the carbonylative coupling with the functionalized aromatic iodide, such a transfer is unnecessary, since the zinc does not react with the electrophile under the reaction conditions. These two protocols also illustrate how to conduct such reactions on different scales. 

It is preferable for relatively inexpensive Ni-based catalysts to be used instead of expensive Pd-based catalysts in the carbonylative polycondensation. However, in the case of carbonylative coupling of dibromoarenes with aromatic diamines, yielding polyaramides, the use of nickel-based catalysts is not so successful for the synthesis of high molecular weight polymers, compared with the method using palladium-based catalysts [166],... 

Explain why carbon-heteroatom carbonylative coupling reactions are preferably carried out with palladium-based catalysts give an example of the catalytic cycle in the carbonylative polycondensation of dihaloarene and bisphenol, leading to a polyester. 

Oxidative coupling was used to form alkyl- and alkoxy-substituted phenanthrenedione products lOOa-d (Table 22) [73]. These compounds can be obtained by other methods, albeit in much lower yields. In this instance, oxidative coupling proceeds even with carbonyl-substituted arenes, and VOF3 gives much better results than thallium- or palladium-mediated coupling procedures. 

When the homocoupling reaction is performed in the presence of carbon monoxide, the palladium-catalyzed carbonylative coupling of organolead compounds takes place (Equation (104)). Thus, organolead triacetates can be carbonylated in the presence of Pd2(dba)3, CHC13 (5 mol%) and NaOMe (5 equiv.) in acetonitrile under atmospheric pressure of carbon monoxide at room temperature to afford good yields of the symmetrical ketones.118... 

Keywords. Organotin compounds. Palladium catalyst. Cross-coupling reaction, Carbonylative coupling... 

In 1979 the reaction of benzyl and aryl halides was reported with mechanistic discussions [8, 9]. The first palladium-catalyzed carbonylative coupling of organic halides with organotin compounds was reported by Tanaka in the same year (Scheme 4) [10,11]. 

Ma W, Li X, Yang J, Liu Z, Chen B, Pan X (2006) A convenient synthesis of aryl ferrocenylethynyl ketones and 2-ferrocenyl-4H-chromen-4-ones via palladium-catalyzed carbonylation coupling. Synthesis 2489-2492... 

The construction of -silyl divinyl ketones in many different structural settings has been weU developed. The four principal connections outlined in Scheme 16 are as follows path a, vinyl organome-tallic addition to 3-trimeAylsilyl-2-propenal path b, 3-trialkylsilylvinyl organometallic" addition to enals path c, palladium-catalyzed carbonylation/coupling of 2-trimethylsilylvinyltrimethylstan-nane and path d, acylation of a B-silyl copper reagent. 

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