Model Studies of Coenzyme B12 Dependent Diol Dehydratase. 1. Synthetic, Physical Property, and Product Studies of Two Key, Cobalt-Bound, Putative Diol Dehydratase Intermediates

Article abstract of DOI:10.1021/ja00364a022

Following a brief introduction to the controversial question of cobalt participation or nonparticipation in the adenosylcobalamin (coenzyme B₁₂) dependent diol dehydratase rearrangement reaction, HOCH2CH2OH -> CH3CHO + H2O, the two key, cobalt-bound, putative diol dehydratase intermediates, Co-CH(OH)CH2OH (1) and Co-CH2CHO (2), are prepared and studied by using the coenzyme B₁₂, Schiff base, model system, RCoX.The first synthesis, in 80percent yield, and isolation of the often postulated, but unproven, intermediate 1 are reported in a carbonate-protected form, , compound 3, (3).Following the full characterization of 3 by 360-MHz 1H NMR, IR, and X-ray crystallography, including its unexpectedly complex solution NMR behavior and the axial 1,5,6-trimethylbenzimidazole binding constant, the MeO^--catalyzed deproptection in MeOH of 3 is described.The resultant rearrangement reaction and complete stoichiometry to 1 equiv of Co^IICl, 0.5 equiv of CH3OCO2CH3 and CH3OCO2^-, and 95 +/- 4percent CH3CHO are reported.The observed stoichiometry and mass and charge balance suggest that a *CH2CHO intermediate is formed, and evidence is presented suggesting that the CH3OH solvent is the H* source, *CH2CHO + CH3OH -> CH3CHO + *CH2OH.Following the examination of several unsuccessful routes, the intermediate expected from cobalt-participation pathways, Co-CH2CHO, was prepared, OHCCH2CoI (7), and found to be reasonably stable as previously observed for all the other known formylmethyl complexes, and, therefore, apparently not an intermediate in the MeO^--catalyzed deprotection and rearrangement reaction of 3.The results of attempts to use seven protecting groups other than carbonate and the relative advantages and disadvantages of carbonate-protected 3 are then summarized and discussed.In the following paper, ^1b a kinetic and mechanistic study of the rearrangement reaction is presented.