One Electron Oxidation of α-Alkylbenzyl Alcohols Induced by Potassium 12-Tungstocobalt(III)ate − Comparison with the Oxidation Promoted by Microsomal Cytochrome P450

Abstract

The chemical and microsomal oxidations of a number of 4‐methoxy substituted α‐alkylbenzyl alcohols 4‐MeOPhCH(R)OH (Eox = 1.6−1.7 V vs SCE) were investigated. Using potassium 12‐tungstocobalt(III)ate, a bona fide one electron oxidant, competition between Cα−H and Cα−Cβ bond cleavage in the intermediate radical cation was observed when the side‐chain alkyl group R was Et (2) and iPr (3). With R = Me (1), only C−H bond cleavage took place, whereas with R = tBu (4) C−C bond cleavage was the exclusive fragmentation process. In contrast, the microsomal oxidation of the two substrates 3 and 4 led in both cases to the exclusive formation of the corresponding ketone. Thus, an electron transfer mechanism appears unlikely for the microsomal oxidation of α‐alkylbenzyl alcohols, even though the oxidation potential of these species is lower than or comparable to that of the active oxidant in the enzyme. A hydrogen atom transfer mechanism is more in line with these results.

Iron porphyrins-catalysed oxidation of α-alkyl substituted mono and dimethoxylated benzyl alcohols

“…When these results are compared with those reported for the oxidation of substrates 1-4 [30], it can be noted that in monomethoxylated aromatic radical cations the C a -C b bond cleavage seems to be more favoured over the C a -H bond cleavage as compared to the dimethoxylated aromatic radical cations. In fact in the oxidation of 2 significant amounts of 4-methoxybenzaldeyde are formed, while in the oxidation of 6 the only product observed is 1-(3,4-dimethoxyphenyl)-1-propanone.…”

“…Co(III)W was prepared using the literature procedure [27] with some modifications [28]. Substrates 1-4 were available from a previous work [30]. Substrates 5-8 were synthesised according to previously described procedures [30]: 1-(3,4-dimethoxyphenyl)-1-ethanol (5) was prepared by reduction of 3,4-dimethoxyacetophenone with NaBH 4 ; 1-(3,4-dimethoxyphenyl)-1-propanol (6) was prepared by reaction of ethylmagnesium bromide with 3,4-dimethoxybenzaldehyde; 1-(3,4-dimethoxyphenyl)-2-methyl propanol (7) and 1-(3,4-dimethoxyphenyl)-2,2-dimethyl propanol (8) were prepared by reaction of 3,4-dimethoxyphenylmagnesium bromide with the appropriate acid chloride (isobutyryl chloride and trimethylacetyl chloride, respectively) followed by reduction with NaBH 4 .…”

“…Reaction products were analysed by GLC, GC-MS and 1 H NMR. The results are reported in Table 3 along with the results of the oxidations of compounds 1-4 available from the literature [30]. In the oxidation of 5 and 6 the only reaction products were 1-(3,4-dimethoxyphenyl)-1-ethanone and 1-(3,4-dimethoxyphenyl)-1-propanone, respectively.…”

Hydrogen abstraction from H‐donor substrates by the 6‐CF3‐benzotriazol‐N‐oxyl radical (TFNO)

“…In fact, under genuine ET conditions, 1 gives a transient 1 .+ intermediate that cleaves the C α -C β bond of the side-chain, and affords the corresponding aldehyde (2) plus tert-butyl radical (Scheme 4). [34] Scheme 4. Products study for reaction of TFNO with probe substrate 1:…”

“…[34] Conversely, under bona fide radical HAT conditions, 1 undergoes cleavage of the C α -H benzylic bond, and produces the corresponding ketone 3 exclusively. [33,34] This clear-cut behaviour makes 1 a significant probe, capable of differentiating the mechanism of an oxidation reaction from product analysis.…”