Electrochemical reactions mediated by vitamin B₁₂ derivatives in organic solvents

Vitamin B₁₂ enzymes, involving the cobalt species as a catalytic center, mediate various isomerization reactions accompanied by carbon-skeleton rearrangements. In order to simulate the catalytic functions of vitamin B₁₂ as exerted in the hydrophobic active sites of enzymes concerned, we have been dealing with hydrophobic vitamin B₁₂ derivatives, which have ester groups in place of the peripheral amide moieties of the naturally occurring vitamin B₁₂. In this work, the carbon-skeleton rearrangements as mediated by hydrophobic vitamin B₁₂ derivatives were investigated under electrochemical conditions. The controlled-potential electrolyses of alkyl halides with various electron-withdrawing groups were carried out, and the electrochemical carbon-skeleton rearrangements proceeded effectively via formation of anionic intermediates. These reactions can also be applied to the ring-expansion reactions. We have prepared a novel vitamin B₁₂ derivative, [Cob(II)7Phe(OBzl)]ClO₄, having phenylalanine residues on the peripheral side chains. [Cob(II)7Phe(OBzl)]ClO₄ effectively catalyzed 1,2-migration of the carboxylic ester in 1-bromo-2,2-bis(ethoxycarbonyl)propane at - 1.0 V vs. SCE under irradiation conditions. A strapped hydrophobic vitamin B₁₂ was prepared in order to change the enantioselectivity, and the controlled-potential electrolysis of a racemic alkyl halide was carried out in the presence of vitamin B₁₂ derivatives. Product analyses and computational calculations suggested that the stability of alkylated complexes dominated the enantioselectivity of reduction products.