Diastereomeric Control in the Formation of Carbon−Cobalt Bonds in Organocobalt Corrinoids:  Reactions of Cobalt(II) Corrinoids with Organic Hydroperoxides¹

Abstract

1,1-Dimethylpropyl hydroperoxide reacts with cobalt(II) cobinamide via a Fenton-like reaction to produce a mixture of the diastereomeric alpha- and beta-ethylcobinamides (CH(3)CH(2)Cbi(+)'s, in which the organic ligand is in the "lower" or "upper" axial ligand position, respectively), the composition of which depends on the ratio of starting materials. When the hydroperoxide reagent is in excess, <2% of the CH(3)CH(2)Cbi(+) product is the alpha diastereomer, a product distribution which agrees with previous observations of the equilibrium mixture. This distribution apparently arises because the previously demonstrated CH(3)CH(2)(*)-promoted isomerization of CH(3)CH(2)Cbi(+) diastereomers leads to equilibration. However, when cob(II)inamide is in excess over hydroperoxide, the CH(3)CH(2)Cbi(+) product contains 87% alpha diastereomer and 13% beta diastereomer. Evidently, under these conditions, trapping of the CH(3)CH(2)(*) radical is sufficiently rapid to prevent the radical-induced isomerization of diastereomers and a kinetically controlled product distribution results. This condition has been used to study the relative energetics of kinetically controlled alpha and beta alkylation of cob(II)inamide by CH(3)CH(2)(*). For cob(II)inamide itself, the alpha diastereomer is enthalpically stabilized relative to the beta diastereomer in the transition state for carbon-cobalt bond formation, but an even larger entropic stabilization of the beta diastereomer causes the latter to be the predominant product. The entropic preference for the beta diastereomer is shown to be the result of the differential side chain configurations at the alpha and beta faces of the cobalt corrinoids by experiments with side-chain-altered analogs. When the downwardly projecting f side chain is enlarged by esterification of the N-methylated nucleotide 1-alpha-D-ribofuranosyl-3,5,6-trimethylbenzimidazole 3'-phosphate, the proportion of the alpha diastereomer in the alkylated product drops to 74% and the effect is due solely to an increased entropic preference for the beta diastereomer. Similarly, when the normally downwardly projecting e propionamide side chain is epimerized to the upward (beta) face of the corrin, the proportion of the alpha diastereomer in the product is increased to 95% and the effect is entirely entropic again. Taken together with previous work, the results lead to a general picture of the energetics of alkyl radical + cobalt(II) corrinoid combination reactions and their microscopic reverse, the homolytic dissociation of carbon-cobalt bonds, a rare instance in which the subtleties of such diastereomeric control can be understood at a very fundamental level.

Kinetics and Mechanism of the Reversible Binding of Nitric Oxide to Reduced Cobalamin B12r (Cob(II)alamin)

“…In addition, the rapid spectral changes observed in the laser flash experiment at this pH were followed by an approximately 20 times slower process (dotted lines in the spectrum presented in Figure a). The nature of this process was not fully investigated (our main interest being the reaction occurring under physiological conditions, i.e., at pH 7.4), but on the basis of the experimental observations it may be ascribed to the photoinduced formation of α-nitrosylcobalamin, in which the nitrosyl ligand is coordinated at the α site of the corrin ring 3 Transient spectra recorded in the laser flash photolysis of nitrosylcob(II)alamin in the pH range 1−7.4.…”

“…(a) Support for such an explanation comes from the following observations: (i) the slower process was observed at pH < 4, i.e., where the α-DMBI ligand is protonated and does not coordinate to cobalt at the α-site of the corrin ring;23b (ii) substitution of NO at the more crowded α-site of the corrin ring may be slower than the formation of the β-diastereoisomer, exhibit pseudo-first-order kinetics in the presence of excess NO and depend on the free NO concentration; all of these points are in line with our experimental observations; (iii) the spectral changes for the slower reaction are similar to those observed in the fast process (i.e., formation of the β-nitrosylcobalamin) but shifted to longer wavelengths; thus, the electronic spectrum of the compound formed in the slower reaction exhibits a red-shift typically observed for α-diastereoisomers of alkylcobalamins;23c (iv) evidence for the formation of small amounts of α- nitrosylcobalamin under acidic conditions (pH < 5) was also provided by 1 H- and 15 N NMR spectroscopy.…”