Hydroxylation benzylic position

The efficiency of reduction of benzophenone derivatives is greatly diminished when an ortho alkyl substituent is present because a new photoreaction, intramolecular hydrogen-atom abstraction, then becomes the dominant process. The abstraction takes place from the benzylic position on the adjacent alkyl chain, giving an unstable enol that can revert to the original benzophenone without photoreduction. This process is known as photoenolization Photoenolization can be detected, even though no net transformation of the reactant occurs, by photolysis in deuterated hydroxylic solvents. The proton of the enolic hydroxyl is rapidly exchanged with solvent, so deuterium is introduced at the benzylic position. Deuterium is also introduced if the enol is protonated at the benzylic carbon by solvent ... 

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. 

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

Appreciably high ee-values were also observed in a series of hydroxylations at benzylic positions in all cases predominantly leading to the (R)-configured alcohol [115]. With tetrahydronaphthalene as substrate the best result was obtained 72% ee, 47% yield. 

The hydroxylation of aliphatic C-H bonds can be performed exclusively by CPO [65-67]. A direct oxygen transfer mechanism has been suggested, as the oxygen atom arises from the peroxide. The reaction requires an activated C-H bond since hydroxylation occurs at the ally lie or benzylic positions. Both cyclic (cyclohexene)... 

Reactions of the alkaloids lythrine (15 R = H) and lythridine (17) have been studied (Scheme l).17 Mercuric-acetate-induced stereoselective addition to the unsaturated lactone group of lythrine (15 R = H) results in introduction of a methoxy-group at the benzylic / -position to give a product (16) that is epimeric at C-13 with the hydroxylated alkaloids, cf. (17). Benzylic substituents undergo ionization and trapping with solvent to give more stable epf-products cf (17) - (16). 

Hydroxylation at the benzylic position is encountered very rarely. An example is the oxidation of 10-methylanthrone to lO-hydroxy-lO-methyl-anthrone in 67% yield on treatment with 30% hydrogen peroxide in 10% sodium hydroxide in hot ethanol for 3 min (equation 164) [1126]. 

Conversion to benzoate ester 96, obtained by conversion of 94 into the corresponding acid chloride 95 followed by addition of alcohol 91, then set the stage for macrolide formation. This cyclization was effected by deprotonation and intramolecular alkylation at the benzylic position in 41% yield. Desulfurization and concomitant reduction of the olefin then provided 0-methyl lasiodiplodin (97) in 68% yield. Although Tsuji was readily able to construct the six-membered ring at the proper oxidation level, the symmetry implicit in this strategy precluded the required differentiation of the phenolic hydroxyl groups. 

Thus, benzocycloalkenes have been described to undergo bacterial hydroxylation by the Pseudomonas putida strain UV4. As shown in Fig. 16.1-15, this yielded exclusively hydroxylation at the benzylic position, and also one single enantiomer, i.e. the (R)-alcohol. The biotransformation of benzocyclobutene proved, however, to be different from that observed for higher benzocycloalkenes, presumably because of its particular chemical reactivity 77. A similar result has been observed by Holland and coworkers in the course of chroman biotransformation by the fungus Mortierella isabellina[78 which leads, although in low yield, to the benzylic (R)-alcohol. 

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