Preparation and Reactivity of Hydrophobic Vitamin B12 Derivatives Having an Intramolecular Axial Base

In order to clarify crucial roles of an intramolecular axial base in alkylation and dealkylation reactions of vitamin B12, hydrophobic vitamin B₁2 derivatives bearing a proximal base capable of coordinating to the nuclear cobalt at the α - and β-sites, [Cob(II)(α -Im)6 C₁ester]ClO₄ and [Cob(II)(β -Im)6 C2ester]C1O4, respectively, and a hydrophobic vitamin B12 capped with a fragment involving the imidazolyl moiety, [Cob(II)(Im: cap)5 C₁ester]C1O4, were prepared. Their ESR spectra indicated that the three different imidazolyl moieties were completely coordinated to the nuclear cobalt, and such intramolecular coordination acted to shift the Co(II)/Co(I) redox potential to a cathodic side. The extent of potential shift was comparable to that observed upon addition of N-methylimidazole to a hydrophobic vitamin B12 without an axial base at a 50: 1 molar ratio. The axial base did not significantly show a kinetic effect on the alkylation of hydrophobic vitamin B12s, since the univalent cobalt has no detectable tendency to interact with an axial ligand. The imidazolyl segment introduced into the β-site inhibited alkylation reactions due to steric reasons. All the intramolecular axial bases treated in this study enhanced cleavage of the cobalt-carbon bond under aerobic irradiation conditions as originated from their steric and electronic effects.