CHEMISTRY OF COBALAMINS AND RELATED COMPOUNDS .48. STERICALLY INDUCED, SPONTANEOUS DEALKYLATION OF SECONDARY ALKYLCOBALAMINS DUE TO AXIAL BASE COORDINATION AND CONFORMATIONAL-CHANGES OF THE CORRIN LIGAND

The synthesis of various previously inaccessible secondary alkyl-and cycloalkylcobalamins by the reactions of olefins, alkyl iodides, and bromides with hydridocobalamin is described. The coordination of the axial 5, 6-dimethylbenzimidazole ligand of alkylcobalamins is dependent on the steric bulk of the alkyl moiety and most secondary alkylcobalamins exist predominantly in the “base-off” form in neutral solution. Secondary and higher primary alkylcobalamins undergo sterically induced spontaneous dealkylation by way of syn β-elimination, the reverse of the reaction of hydridocobalamin with nonactivated olefins. They are generally more stable in acidic media, in which the axial base is protonated, while in neutral or alkaline solution axial coordination of this base causes a conformational change of the corrin ligand which accelerates the Co-C bond cleavage by orders of magnitude. © 1979, American Chemical Society. All rights reserved.