Regioselectivity aromatic halogenation

When used with A-chloro-, A-bromo-, and A-iodosuccinimide, iron(III) chloride catalyzes the introduction of halogens into arenes. The reaction works well even with deactivated aromatic rings but in some cases the regioselective course is difficult to control (Scheme 39) [49]. 

Peroxidases have been used very frequently during the last ten years as biocatalysts in asymmetric synthesis. The transformation of a broad spectrum of substrates by these enzymes leads to valuable compounds for the asymmetric synthesis of natural products and biologically active molecules. Peroxidases catalyze regioselective hydroxylation of phenols and halogenation of olefins. Furthermore, they catalyze the epoxidation of olefins and the sulfoxidation of alkyl aryl sulfides in high enantioselectivities, as well as the asymmetric reduction of racemic hydroperoxides. The less selective oxidative coupHng of various phenols and aromatic amines by peroxidases provides a convenient access to dimeric, oligomeric and polymeric products for industrial applications. 

FADH2 halogenases such as tryptophan 7-halogenase have been shown to catalyze regioselective halogenation of a wide range of indole derivatives and aromatic heterocycles, where a cofactor regeneration system has recently been developed to use only a catalytic amount of cofactors (Scheme 7.13) [52, 53]. 

A simple synthesis of 3-substituted and 23-disubstituted 4-chloiofuians was accomplished. It involves a CuCl/bipy-catalyzed regioselective cyclization of l-acetoxy-2.22-trichloroethyl allyl ether followed successively by dechloroacetoxylation with Zn dust and tandem dehydro-halogenation-aromatization with tBuOK/18-crown-6 <99CC2267>. 

When a hetero atom, such as N, O, S,259 or a halogen,260 is present in a molecule containing an aromatic ring or a double bond, lithiation is usually quite regioselective.261 The lithium usually bonds with the sp2 carbon closest to the hetero atom, probably because the attacking species coordinates with the hetero atom.262 In the case of aromatic rings this means attack at the ortho position.263 Two examples are... 

By means of an orfho-lithiation of suitably functionalized aromatics it is possible to obtain aryllithium compounds from halogen-free aromatics in a way and with a regioselectivity (Section 5.3.1) for which there is no analogy in the preparation of aryl Grignard reagents. 

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