Cobalamins and Cobinamides
David Dolphin, Halko, D.J., and Silverman, R.B.
Inorganic Syntheses,"D.H. Busch, Ed., John Wiley & Sons, New York, Vol. XX,
Methylcobalamin (I, R = -CH3) and the vitamin B12 coenzyme (I, R = 5'- deoxyadenosyl) are the only known naturally occurring organometalhc compounds. Both are derivatives of vitamin B12 (cyanocobalamin, I, R = —CN) and both can be synthesized from B12 but are best prepared from hydroxocobalamin. These and numerous other derivatives of B12 containing a cobalt-carbon bond are known, and provided the cobalt is bonded to a primary carbon atom the complexes are thermally very stable, but always photochemically labile as a result of homolytic cleavage of the cobalt-carbon bond. Two principal methods for formation of the cobalt-carbon bond are used.The first involves alkylation of B12s (where the cobalt 3+ of B12 has been reduced to Co(l+)) with a primary alkyl halide, or tosylate, or Michael addition of B12s, to an alkyne or activated alkene. While a wide variety of reducing agents will bring about the two-electron reduction of B12 to B12s, sodium tetrahydroborate is recommended for simplicity and reproducibility. However, reduction of the commercially available cyanocobalamin may in some cases present problems when the cyanide displaces the alkyl from the cobalamin during work-up. This problem is readily overcome by using hydroxocobalamin (I, R = —OH) that is prepared from cyanocobalamin by way of methylcobalamin.