FACILE ALPHA/BETA DIASTEREOMERISM IN ORGANOCOBALT CORRINOIDS - STUDIES OF THE INTERCONVERSION OF DIASTEREOMERS BY THERMOLYSIS, PHOTOLYSIS, AND COBALT-TO-COBALT ALKYL GROUP TRANSFER

Nonalkylated cobinamides in the Co(III), Co(II), and Co(I) oxidation states have been shown to catalyze the interconversion of alpha- and beta-methylcobinamide (CH3Cbi) by direct cobalt-to-cobalt methyl group transfer. In every case, the final product composition, starting from either diastereomer, is ca. 95% beta-CH3Cbi and 5% alpha-CH3Cbi, the same product distribution obtained by reductive alkylation of combinamide by CH3I. It is consequently concluded that this is the equilibrium product distribution for the CH3Cbi's and that alpha-CH3Cbi and beta-CH3Cbi come to equilibrium during synthesis by reductive alkylation. For all other alkylcobinamides (RCbi's, R = CH3CH2, CF3CH2, NCCH2, CF2H, and CF3), isomerization could not be observed upon treatment with cobinamide in any oxidation state and these cobalt-to-cobalt alkyl group transfers (R not-equal CH3), if they occur at all, are shown to be several orders of magnitude slower than methyl group transfer. The previously reported facile photoinduced isomerization of alpha- and beta-RCbi's is shown to be completely inhibited by a relatively low concentration of the radical trap 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (4-HTEMPO), suggesting that this isomerization requires escape of the alkyl radical and cob(II)inamide from the solvent cage followed by recombination. The proposed mechanism is thus diffusion limited and suggests that the observed ratio of diastereomers, 2-3:1, beta/alpha, regardless of R, represents the kinetically controlled distribution of products for the prototypical RCbi synthesis reaction, the diffusional combination of R. and cob(II)inamide. A thermally-induced isomerization has also been demonstrated for R = CH3, CH3CH2, CF3CH2, NCCH2, and CH3CH2OCH2CH2 at 70-degrees-C, which leads to a final equilibrium distribution of products in which the beta-diastereomer predominates by >10:1 regardless of R. Radical trapping experiments suggest that thermally-induced isomerization probably results from thermal Co-C bond homolysis for R = CH3CH2 and CF3CH2, but that thermally-induced isomerization of the CH3Cbi's probably occurs via cobalt-to-cobalt transfer due to unavoidable trace contamination with nonalkylated cobinamide. It is concluded that reductive alkylation of cobinamide by RX leads to a steady state product distribution which is under neither thermodynamic nor kinetic control, except for R = CH3, for which the diastereomers come to equilibrium via cobalt-to-cobalt methyl group transfer to either cob(I)inamide or cob(II)inamide.