Palladium catalysis iodination

Thioxylation has also been achieved using palladium catalysis, and reaction of 5-iodo-2,4-dimethoxypyrimidine 202 with the arylthiopropyne 201 occurred with loss of the propyne unit and replacement of the iodine by the arylthio group <2000TL7259, 2001T5885>. 

Palladium(0)-catalysed coupling of an orf/to-halophenolic ether (thioether) with a terminal alkyne (or with an alkynylboronic ester ) and ring closure promoted with an electrophile - iodine has been most often used - is an excellent method to make both benzothiophenes °° ° and benzofurans. ortfto-AIkynyl-phenols can be comparably closed with palladium catalysis in the presence of copper(II) halides to give the corresponding 3-halo-benzofurans, ° and ortfto-alkynyl pyridin-2- and -3-yl acetates likewise ring close with iodine, generating furopyridines. ... 

Palladium catalysis promotes the Reformatsky reaction. Heteroaryl iodides are better substrates than bromides and chlorides. Iodine in electrophilic positions in the substrate, but not in the benzenoid position, were active in the Reformatsky reaction (277,278) (Scheme 63). Homo-coupling is the major pathway for iodo derivatives in the benzenoid position, with formation of 3,3 -biquinoline (279) (85CPB4309). 

C-H borylation is a widely used methodology for the synthesis of organoboronates [63-65]. Most of the applications have been presented for the synthesis of aryl-boronates. However, functionalization of alkenes has also attracted much interest [66, 67]. In most applications, iridium catalysis was used. However, in case of alkenes, borohydride forms as a side product of the C-H borylation, which undergoes hydroboration with alkenes. This side reaction can be avoided using palladium catalysis under oxidative conditions. In a practically useful implementation of this reaction, pincer-complex catalysis (Ig) was appHed (Figure 4.17) [51]. The reaction can be carried out under mild reaction conditions at room temperature using the neat aUcene 34 as solvent. In this reaction, hypervalent iodine 36, the TFA analog of 29, was employed. In the absence of 36, borylation reaction did not occur. 

Interestingly, only BiBrj gave quantitative yields of the products 416, while other bismuth(III) halides and Bi(OTf)3 had absolutely no effect for the reported transformation. The aUcenylbismuth derivatives could also be trapped in sUu with iodine or coupled with acyl chlorides in the presence of a palladium catalyst [119]. Addition of organogold compoimds to activated carbon-carbon triple bonds has also been reported to proceed under palladium catalysis [120]. Thus, (PhjPljPdClj or Pd2(dba)j complexes successfully promoted a regioselective syn carboauration of alkynes at ambient temperature (Scheme 10.143). 

Use of other nucleophiles in the presence of an oxidant can install other functionality (Scheme 3.55). While N-halosuccinimides are very effective, other systems, such as iodosobenzene diacetate-halide mixtures, or copper(II) halide salts can be employed. The powerful oxidant oxone can also be used in combination with alcohols, to give ethers (Scheme 3.56). Iodine acetate has been used for C-H activation directed by carboxylic acids (Scheme 3.57). The heteroatom may also be supplied intramolecularly (Scheme 3.58). The use of palladium catalysis can also override the inherent regioselectivity of an arene substrate (Scheme 3.59). 

Amination under palladium-catalysis is possible using hydroxylamines as electrophiles.Bromination and chlorination can be performed with N-halosuccinimides or PhICb, while iodine can be used directly. In case of PhICl2, the catalytic cycle involves palladium(III) intermediates.A diastereoselective method for the iodination of aromatic compounds was used by the Yu group (Scheme 5-196). 

The iodine-zinc exchange of an alkyl iodide with EtjZn is proi oted by the addition of small amounts of copper(I) salts such as CuCN or Cul. Although the exact reason for this copper catalysis is now known, it has been speculated that the presence of copper(I) salts promotes a radical chain-reaction resulting in the formation of a dialkylzinc species (Scheme 9-32) [22b]. Similarly, the addition of other transition metals such as nickel and palladium salts promotes radical reactions. 

The C—I bond is very unstable and more reactive than C—Br, C—Cl and C—F bonds. Iodine is the most expensive of the common halogens and is much less frequently used in synthesis than bromine, chlorine or fluorine. Organometallic reactions proceed with iodinated aliphatic or aromatic compounds more easily than with the other halogens. Noble metal catalysis with palladium complexes is most effective with iodinated compounds. A useful synthetic procedure is the facile reduction of iodinated derivatives under mild conditions. Replacement of iodine by hydrogen at an sp carbon is an exothermic reaction with A// = -25 kJ mol . ... 

In the area of oxidation catalysis, several interesting reactions have been developed by Waser using a Koser-type hypervalent iodine 71 with an incorporated acetylene ligand (Scheme 16.17). Under catalysis with palladium hexafluoroacetylacetonate, nucleopalladation with both a phenol (e.g., 70) and an acid (e.g., 73) followed by oxidative C(sp )-C(sp) coupling led to new products 72 and 74. Initially, this reaction was developed for cyclization of alcohols or acids, respectively. Both five-and six-membered ring cyclization were successfully employed, and a total of 20 examples with 34-82% yield demonstrate the broad scope of this approach [58]. 

Cisoid retinoids have been isomerized to give the corresponding trans compounds by catalysis with iodine (Cainelli etal, 1973 Reif and Grassner, 1973). Methyl (13Z)-retinoate (176) has been converted to (all- )-retinoic acid (3) by being treated at room temperature with potassium amide in toluene and hydrolysis of the product obtained (Matsui, 1962). Homogeneous catalysis of a mixture of (9Z)-retinyl acetate (366) and (all- )-retinyl acetate (9) in the presence of palladium(II) chloride/acetonitrile adducts gave, by isomerization, a mixture more concentrated in (9), and pure (all- )-retinyl acetate (9) was then isolated in crystalline form from the latter mixture (Stoller and Wagner, 1975 Fischli et al., 1976). 

Various salts such as hypervalent iodines [69] aryldiazonium salts [70] and sulfo-nium salts [71] undergo facile StUle coupling. Acetates [72], carbonates [73] and phosphates [74] are also quite reactive. Finally, heteroaromatic tioethers [75] and sulfonyl chlorides [76] were recently reported to couple under palladium-catalyzed copper-mediated catalysis. 

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