Ortho-iodophenols

Some early examples involving microwave-assisted solvent-free Sonogashira couplings using palladium powder doped on alumina/potassium fluoride as catalyst were described by Kabalka and coworkers (Scheme 4.4) [150], In addition, this novel catalytic system has been used in microwave-assisted solvent-free Sonogashira coupling-cyclization of ortho-iodophenol with terminal alkynes, and similarly of ortho-ethynylphenols with aromatic iodides, to generate 2-substituted benzo[b]furans... 

The regioselectivity in certain aromatic chlorinations by hypochlorite is also pH-depen-dent. The ortho/para ratio in phenol chlorination increased from 0.64 at pH = 4 to 4.3 at pH = 10794. Selective 4-chlorination of phthalic acid is obtained in aqueous sodium hypochlorite solution795. Iodination of phenols in aqueous systems is also pH-dependent and the ortho iodophenol yield grows at stronger basic media796,797. 

In the laboratory of M. Nilsson, a facile one-pot synthesis of isocumestans (6H-benzofuro[2,3-c][1]benzopyran-6-ones) was developed via a novel extension of the Castro-Stephens coupling utilizing ortho-iodophenols and ethyl propiolate. The reaction can be regarded as an extended Castro-Stephens coupling where an intermediate cuprated benzofuran couples with a second equivalent of ortho-iodophenol, and the product lactonizes to isocumestan. 

These annulations can be extended bqrond indole syntheses. For example, the analogous reaction with ortho-iodophenols can provide an effective method to build up benzofurans (Scheme 6.50) [67]. Presumably due to the lower nudeophilicity of the phenolic oxygen, these reactions generally require higher reaction temperatures. Nevertheless, similar regioselectivity was found here as with the indole synthesis, and, in particular, 2 -silyl-substituted benzofuran is often obtained with high selectivity. This same approach can be applied to the construction of pyrroles and furans [68]. 

The synthesis of benzofurans and related compounds from ortho-iodophenol and copper] I) acetylides via a coupling-cydization reaction (vide infra) was introduced by Castro in the 1960s [75-77] and stimulated the development of many contemporary transition metal-catalyzed synthetic approaches toward the assembly of the benzofuran unit. In a subsequent report from Castro s group, it was proposed that the formation of the benzofuran core occurs in a stepwise fashion with the intermediacy of ortho-alkynylphenol, which, upon activation by the Cu(I) salt promoter, undergoes subsequent cydoisomerization [77]. 

More recently, Bolm reported that the 3 + 2 synthesis of benzofurans from terminal alkynes and ortho-iodophenols could be achieved with a moderate efficiency in the presence of the FeCh-DMEDA [122] catalytic system [123]. 

More recently, Emrich and Larock [33] reported the first catalytic oxyarylations of chromens by ortho-iodophenols in DMF in the presence of 5 mol% of Pd(OAc)2/ Na2C03, later ejctending this methodology to other cyclic olefins. Kiss et al. [34] also reported the Pd(OAc)2-catalyzed oxyarylation of O-6-benzyloxy-chromen by ortho-iodophenol in acetone in the presence of Ag2C03 and PPh3, but the scope of this reaction with other olefins and ortho-iodophenols has not yet been investigated. 

A spore-forming strain of Desulfitobacterium chlororespirans was able to couple the dechlorination of 3-chloro-4-hydroxybenzoate to the oxidation of lactate to acetate, pyruvate, or formate (Sanford et al. 1996). Whereas 2,4,6-trichlorophenol and 2,4,6-tribro-mophenol supported growth with the production of 4-chlorophenol and 4-bromophenol, neither 2-bromophenol nor 2-iodophenol was able to do so. The membrane-bound dehalogenase contains cobalamin, iron, and acid-labile sulfur, and is apparently specific for ortho-substituted phenols (Krasotkina et al. 2001). 

V(Ce, X) populations are close to their values in the corresponding halobenzene however, there is a small electron transfer towards this basin for X = F, whereas the iodine atom undergoes an opposite effect. With respect to phenol, the regioselectivity of the electrophilic substitution is softened because as the OH and X = F, Cl, Br groups are both ortho-para directors, they contribute in opposite directions. As all the positional indices of CeHsI are positive, they are enhanced in the trans orf/io-iodophenol. The additive rule works satisfactorily for all positions as the largest discrepancy between estimated and calculated value does not exceed 0.002. 

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