Aryl complexes, iodide substitution

The reaction was successfully carried out with various aryl(hetaryl) iodides and bromides involving different aryl thiols and alkyl thiols. A plausible catalytic cyde includes reduction of Co(II) complexes to Co(I), substitution of iodide ligand by SR leading to the formation of ArSCo(I), oxidative addition of ArX to this cobalt complex with formation of Co(III) derivative, followed by reductive elimination (Scheme 3.57) resulted in the product formation and regeneration of Co(I) catalyst. 

Copper(I) complexed with 1,10-phenanthroline has been used in the arylation of imidazo[l,2-a]pyridines by aryl bromides, iodides, and triflates to give products, (139), substituted at the 3-position. The mechanism is likely to involve initial deprotonation at the 3-position followed by cupration and oxidative addition of the aryl halide. The copper-mediated cross-coupling of indoles with 1,3-azoles is assisted by chelation of a, readily removed, 2-pyrimidyl group and leads to products such as (140). In this reaction, two carbon-hydrogen substitutions are required and it is likely that initial cupration of the 1,3-azole is followed by chelation-assisted formation of a bis(heteroaryl) copper species before oxygen-promoted reductive elimination... 

Mercuration of aromatic compounds can be accomplished with mercuric salts, most often Hg(OAc)2 ° to give ArHgOAc. This is ordinary electrophilic aromatic substitution and takes place by the arenium ion mechanism (p. 675). ° Aromatic compounds can also be converted to arylthallium bis(trifluoroacetates), ArTl(OOCCF3)2, by treatment with thallium(III) trifluoroacetate in trifluoroace-tic acid. ° These arylthallium compounds can be converted to phenols, aryl iodides or fluorides (12-28), aryl cyanides (12-31), aryl nitro compounds, or aryl esters (12-30). The mechanism of thallation appears to be complex, with electrophilic and electron-transfer mechanisms both taking place. 

Very recently another highly active and well-defined Pd-NHC based pre-catalyst containing a cyclopentadienyl (Cp) ligand 18 has been successfully applied in this transformation. Cp was chosen as stabilising ligand due to its well-known tendency to reductively be removed from Cp-Pd complexes that may help in the transformation of the pre-catalyst into the desired catalytic active species (NHC)Pd(O) [107]. Di- and tii-ortho substituted biaryls were obtained in good to excellent yields however, when the formation of tetra-orf/to substituted compounds was attempted very poor yields were obtained, even using aryl bromide or iodide substrates (Scheme 6.28). 

The first examples of NHC-Pd complexes applied to the Sonogashira reaction were reported to show a limited scope in the coupling of aryl iodides and activated aryl bromides with acetylene [23,33,52]. However, the use of A-carbamoyl-substituted heterocyclic carbene Pd(ll) complexes expanded the use to alkyl-acetylenes and deactivated aryl iodides and bromides [124] (Scheme 6.40). 

Recently, Larock and coworkers used a domino Heck/Suzuki process for the synthesis of a multitude of tamoxifen analogues [48] (Scheme 6/1.20). In their approach, these authors used a three-component coupling reaction of readily available aryl iodides, internal alkynes and aryl boronic acids to give the expected tetrasubsti-tuted olefins in good yields. As an example, treatment of a mixture of phenyliodide, the alkyne 6/1-78 and phenylboronic acid with catalytic amounts of PdCl2(PhCN)2 gave 6/1-79 in 90% yield. In this process, substituted aryl iodides and heteroaromatic boronic acids may also be employed. It can be assumed that, after Pd°-cata-lyzed oxidative addition of the aryl iodide, a ds-carbopalladation of the internal alkyne takes place to form a vinylic palladium intermediate. This then reacts with the ate complex of the aryl boronic acid in a transmetalation, followed by a reductive elimination. 

Aryl- and alkylsulfonyl radicals have been generated from the corresponding iodides and added to, e.g., propadiene (la), enantiomerically enriched (P)-(+)-propa-2,3-diene [(P)-(lc)] and (P)-(-)-cyclonona-l,2-diene [(P)-(lk)] [47]. Diaddition of sulfo-nyl radicals may compete considerably with the monoaddition [48,49]. Also, products of diiodination have been purified from likewise obtained reaction mixtures, which points to a more complex reactivity pattern of these substrates towards cumulated Jt-bonds. An analysis of regioselectivities of arylsulfonyl radical addition to allenes is in agreement with the familiar trend that a-addition occurs in propadiene (la), whereas alkyl-substitution at the cumulated Jt-bond is associated with a marked increase in formation of /3-addition products (Scheme 11.7). 

The utility of a palladium catalyst in the synthesis of substituted aryl acetylenes is well established.(7,8,9,10) The end-capping agent I was produced by using a standard catalyst system, dichlorobls(triphenylphosphlne)palladlum (II)/copper (I) iodide/triphenylphosphlne mixture, which has been employed in previously developed ethynylation procedures.(10) The copper (I) iodide is believed to act as a cocatalyst, reducing the palladium (II) complex to the active palladium (0) catalyst. The scheme is shown in Figure 3 (diethylamine is the solvent).(11)... 

A very convenient method for the selective preparation of aNHC complexes is to block the imidazolium ligand precursors by substitution at C2 with alkyl or aryl groups [29, 30]. Following this procedure, the coordination of 1,2,3-trimethylimid-azolium iodide to [Cp IrCl2]2 afforded Cp Ir(aNHC), as shown in Scheme 3.14 [31]. 

As an alternative to addition of anionic nucleophiles followed by reoxidation, rhodium(l)-catalyzed C-H activation allowed the nucleophilic addition of alkenes to the intermediate Rh(i) carbene complex <2002JA13964, 2004JOC7329>. Purine behaved anomalously compared to other heterocycles, for which selective monoalkylation was observed, and underwent sequential substitution first at C-8 and then at C-6 (Equation 8). Caffeine was monoalkylated at C-8 in low yield (15%). Selectivity for C-8-arylation was also observed in the palladium-catalyzed C-H activation of 6-phenyl-9-benzylpurine (aryl iodides, 0.05 equiv Pd(OAc)2, 3 equiv Cul, 2.5 equiv CS2CO3, DMF, 160 °C, 60 h, 48-95% yields) <2006OL5389>. 

Normally, the most practical vinyl substitutions are achieved by use of the oxidative additions of organic bromides, iodides, diazonium salts or triflates to palladium(0)-phosphine complexes in situ. The organic halide, diazonium salt or triflate, an alkene, a base to neutralize the acid formed and a catalytic amount of a palladium(II) salt, usually in conjunction with a triarylphosphine, are the usual reactants at about 25-100 C. This method is useful for reactions of aryl, heterocyclic and vinyl derviatives. Acid chlorides also react, usually yielding decarbonylated products, although there are a few exceptions. Likewise, arylsulfonyl chlorides lose sulfur dioxide and form arylated alkenes. Aryl chlorides have been reacted successfully in a few instances but only with the most reactive alkenes and usually under more vigorous conditions. Benzyl iodide, bromide and chloride will benzylate alkenes but other alkyl halides generally do not alkylate alkenes by this procedure. 

Ullmann reaction (4, 33-34). Semmelhack et al.1 recorded details of the coupling of aryl and vinyl halides with Ni(0) complexes, (COD)2Ni or Ni[P(C6H5)3]4. This reaction was used for the first synthesis of almusone (3), an antileukemic lignan obtained from the wood of Alnus japonica Steud. In the case of ort/io-substituted aryl iodides such as 1, reduction becomes a competing reaction and the yields are only moderate. In fact o,o-disubstituted aryl halides cannot be coupled under these conditions. Deliberate addition of a proton source increases formation of the reduction product. Acetic or trifluoroacetic acid are useful for this purpose. Added triphenyl-phosphine also promotes reduction. 

There is continued expansion in the use of metals as catalysts in substitution reactions. Copper iodide in the presence of /V./V -dimcthylcthylcncdiamine has been shown to be effective in the intramolecular substitution of aryl bromides carrying an o-l,3-dicarbonyl substituent reaction may involve either an oxygen centre or a carbon centre of the dicarbonyl moiety.26 The reaction of aryl halides with sodium trifluoroacetate in the presence of copper iodide may lead to the formation of the tri-fluoromethylated derivatives, possibly via CF3CuI as an intermediate.27 There have been theoretical calculations, PM3 and ab initio, on complexes formed from copper... 

---