Cobaloxime Substitution Reactions

Cobalamin and Cobaloxime Substitution Reactions.— The substitution kinetics of vitamin Biaa with 8-azaguanine and 6-mercaptopurine have been investigated in aqueous media at 25 °C and ionic strength 0.1 M. The complex pH dependences are interpreted in terms of reactions of the base on aquocobalamin with protonated and deprotonated forms of the ligands. Rate constants are listed in Table 7 and are consistent with a dissociative interchange mechanism. A similar mechanism is likely in the substitution reaction of cyanocobalamin with [Fe(CN)e] . Both base on and base off forms of the coenzyme are reactive. 

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CONTENTS Preface, Mark Lautens. Photocyclization and Photocycloaddition Reactions of 4- and 2-Pyrones, Frederick G. West. Intramolecular [4+3] Cycloaddition Reactions, Michael Harmata. Lewis Acid Catalyzed [2+2] Cycloaddition Reactions of Vinyl Sulfides and Their Analogues Catalytic Asymmetric [2+2] Cycloaddition Reactions, Koichi Narasaka and Yujiro Hayashi. Vinylboranes as Diels-Alder Dienophiles, Daniel A. Singleton. Preparation and Exo-Selective [4+2] Cycloaddition Reactions of Cobaloxime-Substituted 1,3-Dienes, P... 

It is generally believed that the cobalt-carbon a-bond is rather unstable and reactive. However, cobaloximes, model complexes of vitamin B12, form simple alkylcobaloximes by several ways, such as reductive alkylation, addition of olefins, and substitution reaction. The cobalt-carbon bonds thus formed are surprisingly stable, and undergo a variety of cleavage reactions, such as/3-elimination, coupling, substitution with nucleophiles, and other reactions. The effect of this specific ligand is remarkable. 

Comparison of the activation parameters with those for the corresponding reactions of the aquocobalamin suggest that the lability of the biological complex arises mainly because of entropy effects. The substitution reactions of aquocobalamin are quite rapid and the rate constants are nearly independent of the nature of the incoming ligand. When an alkyl group is present in the axial position in the cobaloximes and the related complex (20) the substitution of the water ligand in the trans position is also very rapid and involves a dissociative mechanism. 

Vinylallenes can be hydrometallated to produce 1-cobaloxime-substituted dienyl complexes (Equation (25)). Cobaloxime-substitued 1,3-diene without a substituent in the 3-position will participate in thermal and Lewis acid-catalyzed Diels-Alder reactions, but the resulting cycloadducts apparently rearrange and give products with... 

A number of papers have been concerned with substitution reactions of Vitamin B12 model compounds. Kinetics of the substitution of the alkylaquo-l,3-bis(acetyl monoximeimino)propanato-cobalt ions (MH2O) by L are consistent with formation of an intermediate MH20,L only when L contains an aromatic group. Sjxl substitution reactions of the axial aquo-ligand in methyl aquo-cobaloxime by thiols, primary amines, and 4-substituted pyridines have been described. 

Steric factors play an important role in reactions of bromomethylaqua-cobaloxime with substituted imidazoles - 1-methylimidazole reacts at approximately the same rate as imidazole itself, but the presence of an alkyl substituent in the 2-position of the incoming imidazole reduces the rate dramatically (72). 

Sh2 and Sh2 reactions have been devised to prepare sulfides or sulfones. The former ones are limited to highly strained carbocyclic compounds [6d-e, 76]. The latter ones are more common, and various vinylic or allylic derivatives including stan-nanes and cobaloximes are known to react with sulfur-centered radicals [77]. A representative example is shown in Eq. (32), where the three-membered ring in IH-cyclopropabenzene opens upon attack by various thiyl radicals to give the corresponding ort/zo-substituted toluenes. 

In view of the reversibility of / -elimination reactions in the chemistry of substituted alkylcobalamins and -cobaloximes and the potential biochemical importance of such reactions, we will now discuss the mechanism of these remarkable reactions (9). 

Finally, some successful reductive arylations have been reported via reaction of aryl halides with cobalt(I) nucleophiles. Generally speaking these reactions are only successful when the aryl halide has an electron-withdrawing substituent and yields are generally less than 15% [58,59]. Thus, pyridinecobaloxime(I) reacts with p-bromoacetophenone, methyl-m- and methyl-/>-bromobenzoate, and p-bromo-a,a,a-trifluorotoluene, to produce the expected substituted phenyl(pyridine)cobaloximes in yields of 11.5, 10, 7, and 5% respectively. 

Cobalt(i).—The main interest here is in cobaloximes and similar cobalt(i) chelate complexes as models for reduced forms of vitamin Big. Kinetic studies of alkylation at cobalt(i), as in the recent study of reaction of alkyl halides with, for example, cobaloximes and vitamin Bias, indicate an 5 n2 mechanism, with cobalt(i) acting as a very strong nucleophile. The 5 n2 mechanism has now been confirmed stereochemically by establishing that these reactions proceed with inversion of configuration at carbon. Reaction of vinyl halides with these cobalt(i) complexes also proceeds by an associative nucleophilic substitution mechanism, rather than via acetylenic intermediates. ... 

A detailed study of the reactions between alkynyl or vinyl halides and [Co(dmgH)2py] has demonstrated a complex pattern of behaviour (Cooksey et al., 1972). At low concentrations of nucleophile over short reaction times, the reaction with prop-2-ynyl halides yields the prop-2-ynylcobal-oxime, presumably by a nucleophilic displacement pathway. However, at longer reaction times in the presence of an excess of cobaloxime, allenyl-cobaloxime is observed. This is formed as a consequence of an 8 2 displacement of one cobaloxime by another attacking the initially formed prop-2-ynylcobaloxime as shown in 8cheme 9. The reactions of substituted... 

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