Pyridine reaction with iodobenzene

The Beecham group found that thiols add readily to the double bond of C(2)-unsubstituted 1-carbapenems, and this approach has been used to synthesise racemic PS-5 130). The A -silylated 4-allylazetidinone (157) was alkylated with ethyl iodide and the product (158) transformed to the phosphorane (159). Cyclisation to (1 ) was followed by reaction with acetamidoethane thiol to form three isomers of the addition product (161). These could be converted to the carbapenem (162) on reaction with iodobenzene dichloride in the presence of pyridine. Isomerization to (163) and deprotection afforded the racemic natural product. The ester (163) has also been prepared via the diazo-intermediate (164) derived from the 4-acetoxy azetidinone (165) 131). A total synthesis of chiral PS-5 has been achieved using the resolved acid (166) (132). This was converted to (164) and then to optically pure PS-5. It has also been possible to synthesise PS-5 and PS-7 from the olivanic acid derivatives MM 17880 and MM 13902 133). The benzyl ester of ( )-MM 22381 was obtained from the azabicyc-loheptane (167) derived from the addition of acetamidoethane thiol to the appropriate C(2)-unsubstituted nucleus 108). 

An electrophilic palladation by a phenyl palladium intermediate at C(3) and a C(3) to C(2) migration of a palladium species, followed by reductive elimination, is indicated. 2-Phenylpyridine has been formed by the reaction of pyridine and iodobenzene at 150 °C in the presence of phosphido-bridged ruthenium dimer complexes.49 A catalytic cycle involving one of the complexes in the system was proposed. Optimum conditions for the efficient and regioselective palladium-catalysed C(2) arylation of ethyl 4-oxazolecarboxylate (47) with iodobenzene have been presented.50... 

Depending on the reaction conditions, halogenation of thieno[2,3-Z>]pyridine (20) can lead to a variety of products resulting from substitution, addition, and oxidation reactions. 2,3-Dibromo-thieno[2,3-/)]pyridine is produced by the reaction of compound (20) with bromine in an aqueous carbon tetrachloride system and the 2,3-dichloro-2,3-dihydro derivative is formed from the same starting material upon treatment with chlorine in chloroform/water or with iodobenzene dichloride in aqueous acetonitrile (70JHC81, 71JHC931). 

Zinc derivatives are available by transmetallation reactions as discussed in Section 6.02.5.6.4. Most work has been done with pyridines, but coupling reactions seem equally feasible with pyrimidines. An example is provided by 2-iodo-4,6-dimethylpyrimidine which is zincated in the 2-position and Pd-coupled with iodobenzene to furnish the 2-phenyl derivative in 26% yield <93T9713). 

In small-scale e.xperiments, overnight reaction of lithium dipropenylcuprate with iodobenzene in ether containing 20 equivalents of pyridine at 25° gave 1-propenyl-benzene in 60 % yield. For coupling with aromatic halides, this solvent system is superior either to ethei tetrahydrofuran or to ether containing 4 equivalents of hexamethylphosphoric triamide. 

The relatively stable (arylsulfonylmethyl)iodonium salts 763 (Section 2.1.9.5) are efficient electrophilic alkylating reagents towards various organic nucleophiles (thiophenolate anion, amines, pyridine, triphenyl phosphine and silyl enol ethers). All these reactions proceed under mild conditions and selectively afforded the appropriate product of alkylation along with iodobenzene as the by-product (Scheme 3.299) [1016]. 

Although, examples of the arylation of oxazole itself are Umited, the reaction with 2-chloro-3,6-dialkylpyridazines at the 5-position is known [58]. 2-Phenyloxa-zole [78] and benzoxazole [58, 78,91,92] are good substrates for the direct arylation (Equations 10.58 and 10.59) [78]. The arylation of oxazolo[4,5-fe]pyridine can be carried out under mild conditions (Equation 10.60) [93]. Treatment of ethyl 4-oxazolecarboxylate with iodobenzene in the presence of a catalyst system consisting of Pd(OAc)2 and IMes affords its 2-phenylated product predominantly (Equation 10.61) [94]. The regjoselectivity may be attributable to steric reasons. 

Palladium-catalysed directed C-H oxidation with (diacetoxy)iodobenzene of a series of meta -substituted aryl pyridine and aryl amide derivatives resulted in the formation of the corresponding acetoxy compounds. The reactions generally proceed with high levels of regioselectivity for functionalization of the less sterically hindered ortho-C-H bond.144 The mechanism shown in Scheme 4 has been proposed for the oxidation of 2,6-dimethylphenol with (diacetoxyiodo)benzene for the formation of 3,5,3, 5 -tetramethyl-biphenyl-4,4 -diol, via C-C coupling.145... 

The second special case is formed by the photoreactions of 2,4-dinitro-6-(phenyliodonio)phenolate (266) with several nucleophiles759. Upon irradiation of this fairly stable zwitterion in methanol, 6-methoxy-2,4-dinitrophenol is formed in 65% yield. Photoreaction with pyridine affords 2,4-dinitro-6-pyridiniophenolate (85%) and irradiation in the presence of phenyl isothiocyanate in acetonitrile affords a mixture of two stereoisomeric 2-phenylimino-5,7-dinitro-1,3-benzoxathioles (269) (71%) which could not be separated. The reaction starts with attack of the nucleophile on the positively charged iodine atom, leading to an iodinane (267) and proceeds by expulsion of iodobenzene. The mechanism is illustrated for phenylisothiocyanate, a case in which the substitution product (268) can undergo further photocyclization to a benzoxathiole derivative (269) (equation 196). 

Sulfoxides. Sulfides are converted by a stoichiometric amount of iodobenzene dichloride in aqueous pyridine at —40 to 20° to the corresponding sulfoxides in high yield and uncontaminated with corresponding sulfones.3 There are few reagents that are selective for this purpose. The reaction applies to aliphatic, aromatic, and heterocyclic sulfides. 

Figure 2.23 Reaction of pyridine with methyl iodide log A versus the square root of the internal pressure of the solvent. Solvents are (1) isopropyl ether, (2) carbon tetrachloride, (3) mesitylene, (4) toluene, (5) benzene, (6) chloroform, (7) chlorobenzene, (8) bromobenzene, (9) iodobenzene, (10) dioxane, (11) anisole, (12) benzonitrile, and (13) nitrobenzene. [Reproduced with permission from A.P. Stefani, J. Amer. Chem. Soc., 90,1694, American Chemical Society, (1968).]...

Full details (see Vol. 1, p. 185) of the Japanese work on the preparation of trifluoromethylarenes from trifluoroiodomethane and iodoarenes in the presence of copper powder and a dipolar aprotic solvent have become available, and it appears that the best solvent in some cases is pyridine. This method (but with DMF as solvent) has also been used to prepare the compounds PhR [R = Me03C (CF3)3, CF3 0 (CF2)2, or perfluoro-2-tetra-hydrofurfuryl] in good yields from iodobenzene and the corresponding polyfluoroiodo-compounds. Perfluoroalkyl-copper compounds are very probably involved in such reactions, and the reactions of preformed n-perfluoroheptylcopper in dimethyl sulphoxide with the aromatic carbon-hydrogen bonds of benzene, toluene, p-xylene, nitrobenzene, and chlorobenzene also lead to (perfluoroalkyl)arenes (some replacement of chlorine occurs in the case of chlorobenzene). Homolytic substitution by perfluoro-heptyl radicals, perhaps within the co-ordination sphere of the copper atom,... 

Trimethylsilyl cyanide has widely been used synthetically as a reagent for cyanation. With respect to the Pd-catalyzed reaction, only a few reactions are known. The reaction of substituted iodobenzenes with trimethylsilyl cyanide in the presence of Pd(PPh3>4 provides good yields of the corresponding benzonitriles. The PdCl2/pyridine-catalyzed reaction of phenylacetylene and substituted phenylacetylenes with trimethylsilyl cyanide... 

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