Aryl iodides, conversion

On the aryl iodide conversion was higher than 90% in all cases except in the last one (62%). 

Although a sulfhydryl group generally is not converted to an 5-phenyl thioether, the conversion can be accomplished through the use of a Pd-catalyzed arylation with an aryl iodide. Thiophenol can be used to introduce sulfur into molecules by simple displacement or by Michael additions, and thus, the phenyl group serves as a suitable protective group that can be removed by electrolysis (—2.7 V, DMF, R N X-). ... 

Aryl iodides and fluorides can be prepared from arylthallium bis(trifluor-oacetates) (see 12-21), indirectly achieving the conversions ArH —> Arl and ArH ArF. The bis(trifluoroacetates) react with KI to give Arl in high yields. Aryllead triacetates, ArPb(OAc)3, can be converted to aryl fluorides by treatment with BFs-etherate. ... 

However, given that other, supposedly stable and leach-resistant catalysts that we had previously studied seemed to operate solely by a leaching mechanism, with no supported Pd apparently active for the reaction (vide supra) and that other authors had found precatalysts of this type to operate by solely a leaching mechaiusm in Heck conversions of aryl iodides (19), we decided to investigate this system further using the solid poison testing method. 

Entries 7 and 8 illustrate conversion of diazonium salts to phenols. Entries 9 and 10 use the traditional conditions for the Sandmeyer reaction. Entry 11 is a Sandmeyer reaction under in situ diazotization conditions, whereas Entry 12 involves halogen atom transfer from solvent. Entry 13 is an example of formation of an aryl iodide. Entries 14 and 15 are Schiemann reactions. The reaction in Entry 16 was used to introduce a chlorine substituent on vancomycin. Of several procedures investigated, the CuCl-CuCl2 catalysis of chlorine atom transfer form CC14 proved to be the best. The diazonium salt was isolated as the tetrafluoroborate after in situ diazotization. Entries 17 and 18 show procedures for introducing cyano and azido groups, respectively. 

In Section 8.2.3.2, we discussed arylation of enolates and enolate equivalents using palladium catalysts. Related palladium-phosphine combinations are very effective catalysts for aromatic nucleophilic substitution reactions. For example, conversion of aryl iodides to nitriles can be done under mild conditions with Pd(PPh3)4 as a catalyst. 

For the installation of the pyrrolidinylethanol moiety 10 on the aryl group, we first tested Buchwald s Cu-catalyzed conditions with 10, aryl iodide 12, Cs2C03, Cul and 1,10-phenanthroline at 110°C in toluene to prepare the penultimate 49 [14a], The reaction was very slow, giving only 5-10% conversion even after 2 days. The reaction was faster at higher temperatures but two impurities 50 and 51 were observed (Scheme 5.14). To find the optimal conditions, xylene and diglyme were tested as solvents, lithium, potassium and cesium carbonates were screened as bases and 2,2 -bipyridy], TMEDA and l-(2-dimethylaminoethyl)-4-methylpiperazine were examined as ligands. The optimized protocol was identified as 10mol% of... 

A somewhat related process, the cobalt-mediated synthesis of symmetrical benzo-phenones from aryl iodides and dicobalt octacarbonyl, is shown in Scheme 6.49 [100]. Here, dicobalt octacarbonyl is used as a combined Ar-I bond activator and carbon monoxide source. Employing acetonitrile as solvent, a variety of aryl iodides with different steric and electronic properties underwent the carbonylative coupling in excellent yields. Remarkably, in several cases, microwave irradiation for just 6 s was sufficient to achieve full conversion An inert atmosphere, a base or other additives were all unnecessary. No conversion occurred in the absence of heating, regardless of the reaction time. However, equally high yields could be achieved by heating the reaction mixture in an oil bath for 2 min. 

Equation 11.35 Conversion of aryl iodides into aryl phosphonates. 

The conversion of aryl iodides into aryl phosphonates, a useful precursor to aryl phosphonic acids, was performed in a Teflon autoclave by Villemin [51]. A domestic microwave oven was used for these experiments and the reaction times for classic heating were effectively reduced from 10 h to 4-22 min. The reactivity of iodides was good whereas the use of bromides resulted in lower yields and reactions with tri-flates were very slow (Eq. 11.35). It is notable that the reactions were brought to completion with short reaction times in a non-polar solvent. 

Recently, Borner and coworkers described an efficient Rh-deguphos catalyst for the reductive amination of a-keto acids with benzyl amine. E.e.-values up to 98% were obtained for the reaction of phenyl pyruvic acid and PhCH2COCOOH (entry 4.9), albeit with often incomplete conversion and low TOFs. Similar results were also obtained for several other a-keto acids, and also with ligands such as norphos and chiraphos. An interesting variant for the preparation of a-amino acid derivatives is the one-pot preparation of aromatic a-(N-cyclohexyla-mino) amides from the corresponding aryl iodide, cyclohexylamine under a H2/ CO atmosphere catalyzed by Pd-duphos or Pd-Trost ligands [50]. Yields and ee-values were in the order of 30-50% and 90 >99%, respectively, and a catalyst loading of around 4% was necessary. 

Subsequently, a copper-catalyzed cross-coupling [with substoichiometric amounts of copper(l) iodide and N,N -dimethylethylenediamine (DMEDA)] between aryl halides and sulfoximines was developed [52]. In this case, both aryl bromides and aryl iodides reacted well. For the conversion of the former substrates an in-situ copper-catalyzed aryl Finkelstein reaction [53] had to be performed first, as shown in Scheme 2.1.1.22 for the preparation of 64 starting from bromobenzene (62). 

Unactivated aryl iodides undergo the conversion Arl — ArCHj when treated with tris(diethylamino)sulfonium difluorotrimethylsilicate and a palladium catalyst.131 A number of methods, all catalyzed by palladium complexes, have been used to prepare unsymmetrical biaryls (see also 3-16). In these methods, aryl bromides or iodides are coupled with aryl Grignard reagents,152 with arylboronic acids ArB(OH)2,153 with aryltin compounds Ar-SnR3,154 and with arylmercury compounds.155 Unsymmetrical binaphthyls were synthesized by photochemically stimulated reaction of naphthyl iodides with naphthoxide ions in an SrnI reaction.156 Grignard reagents also couple with aryl halides without a palladium catalyst, by the benzyne mechanism.157 OS VI, 916 65, 108 66, 67. 

An extension of the use of 2-selenienyllithium is its conversion, by treatment with copper iodide, into a copper derivative which has been used to prepare 2-arylseIenophenes by Ullmann reactions with aryl iodides (80JCS(P2)97l). 

The most effective solvents for this reaction are polar aprotic solvents such as acetonitrile, DMF, NMP, or DMSO. Addition of halide salts such as tetra-w-butyl-ammonium bromide strongly facilitates the reaction and enables the conversion of aryl iodides and activated bromides even in the absence of phosphines (Jeffery conditions) [19]. Under these conditions the presence of water was sometimes... 

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