Benzylic ligand hydroxylation

The structural difference imposed by the smaller metal chelate rings in the complex [Cu2(L55)] , five-membered instead of six-membered as in [Cu2(L66)], determine a completely different reactivity behavior with dihydrogen peroxide (107). The complex [Cu2(L55)] , undergoes a ligand hydroxylation reaction in the presence of H2O2, but this occurs at a benzylic position and with much slower rate (Scheme 8). The involvement of a hydroperoxo complex of [Cu2(L55)] has been suggested for this reaction, though no intermediate has been characterized yet. 

Dopamine /3-hydroxylase (D/3H) is a copper-containing glycoprotein that hydroxylates dopamine at the benzylic position to norepinephrine.84 During the attempted crystallization of the bis(hydroxide)-bridged dicopper(II) dimer, a side product was subsequently isolated (complex (63)), revealing intramolecular hydroxylation at a formally benzylic position of the tris(imidazo-lyl)phosphine ligand.85 The copper(II) center has an axially compressed TBP structure. 

Fig. 14.8 Experimental ligand interactions with cytochrome P450 2C family. (A) X-ray structure ofthe sulfaphenazole derivate DMZ in rabbit CYP2C5 at 2.3 A resolution (PDB 1 N5B) from Wester et al. [191]. Only one ofthe two-ligand orientations for DMZ in accord with electron density is shown placing the benzylic methyl group in a 4.4 A distance to the heme iron. (B) X-ray structure of S-warfarin in human CYP2C9 at 2.55 A resolution (PDB 10G5) from Williams et al. [192]. The substrate is situated in a predominantly hydrophobic pocket. This binding mode places the 6- and 7-hydroxylation sites 10 A from the iron (arrow).

Scheme 2 Aliphatic hydroxylation in benzylic position of an ancillary ligand by a bis(/x-...

In 2001, Itoh and coworkers reexplored the mechanism of ortAo-phenol hydroxylations using [ Cu°(L ) 2(02)] " (7, Figure 10). This complex contains a deutero-benzyl-amine moiety, and can undergo hgand auto-oxidation, forming benzaldehyde, through a proton-coupled electron transfer (PCET) reaction with the peroxo ligand. 

Precursor of Useful Chiral Ligands. OPEN is widely used for the preparation of chiral ligands. Organometallic compounds with these ligands act as useful reagents or catalysts in asymmetric induction reactions such as dihydroxylation of olefins, transfer hydrogenation of ketones and imines, Diels-Alder and aldol reactions, desymmetrization of meso-diols to produce chiral oxazolidinones, epoxidation of simple olefins, benzylic hydroxylation, and borohydride reduction of ketones, imines, and a,p-unsaturated carboxylates. ... 

Manganese salen complex catalyzes C—H oxidation of organic molecules with NaOCl or PhIO, giving alcohols . Larrow and Jacobsen observed kinetic resolution in the benzylic hydroxylation . Katsuki and coworkers used the axis chiral salen manganese complexes for the benzyl hydroxylation and ether hydroxylation, and attained higher ee with the ligand possessing (/f,/f)-diamine and (R)-axis chirality (equation 84). ... 

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