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From a Theoretical Concept to Biochemical Reactions: Strain‐Induced Bond Localization (SIBL) in Oxidation of Vitamin E
Author(s) -
Rosenau Thomas,
Ebner Gerald,
Stanger Am,
Perl Sharon,
Nuri Limor
Publication year - 2004
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200400265
Subject(s) - regioselectivity , chemistry , structural isomer , ether , annulation , enthalpy , tocopherol , ring strain , function (biology) , computational chemistry , vitamin e , medicinal chemistry , stereochemistry , ring (chemistry) , organic chemistry , thermodynamics , catalysis , antioxidant , physics , evolutionary biology , biology
The regioselectivity of the oxidation of α‐tocopherol (the main component of vitamin E) to an ortho ‐quinone methide ( o QM) has been explained in the literature mostly by the ill‐defined term “Mills–Nixon effect”. In this paper we describe the preparation of eleven α‐tocopherol derivatives, different from each other by the sum of annulation angles, but keeping the electronic factors unchanged. These compounds underwent Ag 2 O oxidation, forming two isomeric o QMs that were trapped by vinylmethyl ether. It was found that the isomeric product ratio changes smoothly as a function of the annulation angles, not abruptly from one regioisomer to the other on going from five‐ to six‐ and seven‐membered rings, as predicted by the Mills–Nixon effect. The relative amounts of the products were determined at four different temperatures, and assuming that the product ratio represents the relative rates ratio, the relative enthalpy of activations could be obtained. Theoretically (at B3LYP/6‐31G* theoretical level) four different intermediates were considered. Each of these underwent angular angles deformations to model the two regioisomers. At each deformation angle the energy difference between the two intermediates models was correlated to the experimental data for each of the four intermediates. It was found that the angle‐deformed lithium (6‐methyl‐2‐benzylium)phenolate correlated best ( R >0.994) to the experimental data. This study confirms that the regioselectivity of the two isomeric o QMs in the oxidation of α‐tocopherol and related compounds is simply a function of angular strain, best explained by the SIBL (strain‐induced bond localization) model. In addition, this study provides evidence that the highest energy intermediate in the oxidation of vitamin E is a phenolate–benzyl cation.