Cob(I)alamin Differentiating Alkenes During Saturation

The olefins 2, 7, 11 , and 19 , have been reduced using catalytic amounts of cob(I)alamin( I(I) ). During a slow saturation, the catalyst is able to differentiate the two diastereotopic faces of the endocyclic double bonds in 11 (t_1/2 4 h,. cf. Scheme 3) are reduced much faster. A rationalization of the data can be obtained formulating tertiary alkylcobalamins as intermediates. Of the oxime 6 (cf. Scheme 2) and the p- bromobenzoate 23 (cf. Scheme 5) the structures have been determined by X-ray analysis.     

Stabilisation of Methylene Radicals by Cob(II)alamin in Coenzyme B12 Dependent Mutases

Coenzyme B₁₂ initiates radical chemistry in two types of enzymatic reactions, the irreversible eliminases (e.g., diol dehydratases) and the reversible mutases (e.g., methylmalonyl‐CoA mutase). Whereas eliminases that use radical generators other than coenzyme B₁₂ are known, no alternative coenzyme B₁₂ independent mutases have been detected for substrates in which a methyl group is reversibly converted to a methylene radical. We predict that such mutases do not exist. However, coenzyme B₁₂ independent pathways have been detected that circumvent the need for glutamate, β‐lysine or methylmalonyl‐CoA mutases by proceeding via different intermediates. In humans the methylcitrate cycle, which is ostensibly an alternative to the coenzyme B₁₂ dependent methylmalonyl‐CoA pathway for propionate oxidation, is not used because it would interfere with the Krebs cycle and thereby compromise the high‐energy requirement of the nervous system. In the diol dehydratases the 5′‐deoxyadenosyl radical generated by homolysis of the carbon–cobalt bond of coenzyme B₁₂ moves about 10 Å away from the cobalt atom in cob(II )alamin. The substrate and product radicals are generated at a similar distance from cob(II )alamin, which acts solely as spectator of the catalysis. In glutamate and methylmalonyl‐CoA mutases the 5′‐deoxyadenosyl radical remains within 3–4 Å of the cobalt atom, with the substrate and product radicals approximately 3 Å further away. It is suggested that cob(II )alamin acts as a conductor by stabilising both the 5′‐deoxyadenosyl radical and the product‐related methylene radicals.     

Reduction‐Labile Organo‐cob(III)alamins via Cob(II)alamin: Efficient Synthesis and Solution and Crystal Structures of [(Methoxycarbonyl)methyl]cob(III)alamin

An efficient synthesis of Coβ‐[(methoxycarbonyl)methyl]cob(III)alamin ( 6 ) is reported as an example of a new method for the preparation of some easily reducible organo‐cob(III)alamins via the alkylation of cob(II)alamin. The procedure represents a considerable improvement compared to earlier methods that were based on an alkylation of cob(I)alamin. Thus, aquacob(III)alamin chloride ( 5 ⁺?Cl) was reduced to cob(II)alamin ( 4 ), either by controlled potential electrolytic reduction or with an excess of sodium formate as reducing agent. The solution of 4 was then treated with an excess of methyl bromoacetate while being reductively poised potentiostatically or kept reduced by the formate, to give crystalline 6 in a yield of up to 91%. The structure of 6 in aqueous solution was mainly established by the completely assigned ¹H‐ and ¹³CNMR spectra (Table 1). The NOE data (Table 2) were best rationalized by the presence of a single main conformation of the (methoxycarbonyl)methyl ligand. Single crystals of 6 were obtained by crystallization from an aqueous solution, and the crystal structure was determined by X‐ray analysis at cryotemperatures. The NMR and crystallographic data of 6 indicated similar structures in aqueous solution and in the crystal with the (methoxycarbonyl)methyl ligand preferring a ‘southern' orientation in each case.     

Cob(I)alamin as Catalyst. 8th Communication. Cob(I)alamin and Heptamethyl Cob(I)yrinate During the Reduction of α,β-Unsaturated Carbonyl Derivatives

Hydrogen bonds as presented in Figure 2 cannot account for the enantioselective attack of cob(I)alamin ( 4 ( I )) or heptamethyl cob(I)yrinate ( 5 ( I )) on one of the two enantiotopic faces of the substrates. The attack of the strongly nucleophilic 3d orbital is preferentially directed to the re-side of the starting materials with (Z)-configuration and leads, after the highly stereoselective reductive cleavage of the Co, C bond, to saturated products with (S)-configuration in varying enantiomeric excesses (see Schemes 1, 3 and Table 1).     

Aspects of the Reduction of Double Bonds Using Cob (I)alamin as Catalys

The olefinic system in 3β-methoxy-4-cholesten-6 a-ol ( 2 ) is reduced using cob (I)alamin ( 1 ( I ); see Scheme 1) as catalyst, aqueous acetic acid as solvent and metallic zinc as electron source (cf. Schemes 2 and 3). Experimental evidence for an attack of 1 ( I ) on both faces of the double bond is presented. By the same catalyst (1 R)-10, 10-dimethyl-2-pinene- 10-carbonitrile ( 9 ) is first transformed to the menthene derivative 11 (see Schemes 4 and 5). The ring opening is then followed by a fast saturation of the disubstituted olefinic system in 11 , and ultimately the remaining double bond is reduced in a slow reaction. The cis-configurated saturated menthane derivative 16 is the main final product ( 16 / 17 ≈ 10:1).     

Kinetics and mechanism of the reversible binding of nitric oxide to reduced cobalamin B(12r) (Cob(II)alamin)

The reduced form of aquacobalamin binds nitric oxide very effectively to yield a nitrosyl adduct, Cbl(II)-NO. UV-vis, (1)H-, (31)P-, and (15)N NMR data suggest that the reaction product under physiological conditions is a six-coordinate, "base-on" form of the vitamin with a weakly bound alpha-dimethylbenzimidazole base and a bent nitrosyl coordinated to cobalt at the beta-site of the corrin ring. The nitrosyl adduct can formally be described as Cbl(III)-NO-. The kinetics of the binding and dissociation reactions was investigated by laser flash photolysis and stopped-flow techniques, respectively. The activation parameters, DeltaH, DeltaS, and DeltaV, for the forward and reverse reactions were estimated from the effect of temperature and pressure on the kinetics of these reactions. For the "on" reaction of Cbl(II) with NO, the small positive DeltaS and DeltaV values suggest the operation of a dissociative interchange (I(d)) substitution mechanism at the Co(II) center. Detailed laser flash photolysis and (17)O NMR studies provide evidence for the formation of water-bound intermediates in the laser flash experiments and strongly support the proposed I(d) mechanism. The kinetics of the "off" reaction was studied using an NO-trapping technique. The respective activation parameters are also consistent with a dissociative interchange mechanism.     

Oxidative Stabilization of Poly(norbornene) Polymers Prepared by Ring Opening Metathesis Polymerization

Polymers prepared by ring opening methathesis polymerization contain double bonds along the backbone and are susceptible to oxidation during high temperature processing or device operation. To overcome this, we report a simple method to improve the oxidative stability of ROMP based polymers by inclusion of a small percentage of monomer functionalized with a radical scavenger in the feedstock. The oxidation induction temperature was improved from 111°C up to 262°C when 8 mol% of the functionalized comonomer was included in the feedstock. Modest improvements in the thermal decomposition temperature were also observed.     

Oxidative homolysis of organochromium(III) macrocyclic complexes

Summary Organochromium complexes, [CrRL(H₂O)]²⁺] (L = 1,4,8,12-tetraazacyclopentadecane; R = 1°- or 2°-alkyl, or para-substituted benzyl), are oxidized to [CrRL(H₂O)]³⁺, which rapidly decomposes (k ₃ > 10² s^–1) by homolysis of the Cr-C bond. Rate constants of the oxidation of these complexes by [IrCl₆]^2– range from 2.20 × 10^–1 (R = Me) to 4.60 × 10⁵ (R = 4-MeC₆H₄CH₂)dm³ mol^–1 s^–1. A very negative reaction constant (–4.3) is found for the oxidation of para-substituted benzlchromium(III) complexes which, in conjunction with the results of product analysis, indicates a [Cr^III/R^.] type transition state.     

Oxidative coupling of NH isoquinolones with olefins catalyzed by Rh(III)

Rh(III)-catalyzed oxidative coupling reactions between isoquinolones with 3-aryl groups and activated olefins have been achieved using anhydrous Cu(OAc)(2) as an oxidant to give tetracyclic products. The nitrogen atom acts as a directing group to facilitate ortho C-H activation. This reaction can be one-pot starting from methyl benzohydroxamates, without the necessity of the isolation of isoquinolone products. A broad scope of substrates has been demonstrated, and both terminal and internal activated olefins can be applied. In the coupling of N-methylmaleimide, a Wacker-like mechanism was proposed, where backside attack of the NH group in isoquinolones is suggested as a key step. Selective C-H activation has also been achieved at the 8-position of 1-naphthol, leading to an olefination product.     

Dioldehydratase Binds Coenzyme B12 in the “Base-On” Mode: ESR Investigations on Cob(II)alamin

Even in the enzyme-bound state the dimethylbenzimidazole ligand in the dioldehydratase from Salmonella typhimurium remains bound to the cobalt ion in contrast to some coenzyme B₁₂-dependent enzymes. Direct, ESR spectroscopic proof for this “base-on” binding mode was obtained by using a coenzyme in which one of the nitrogen atoms of the dimethylbenzimidazole ligand was ¹⁵N labeled (see schematic representation on the right).     

Cob(I)alamin als Katalysator 2. Mitteilung [1]. Reduktion von gesättigten Nitrilen in wasserfreier Lösung

Cob (I)alamin as Catalyst 2. Communication [1]. Reduction of Saturated Nitriles in Anhydrous Solution Using cob (I)alamin as homogenous catalyst in glacial acetic acid saturated nitriles are reduced following the path of a reductive amination. The results prove the presence of an intermediate imine during the reduction of saturated nitriles with cob (I)alamine.     

Mild and Efficient Ring Opening of Epoxides Catalyzed by Potassium Dodecatungstocobaltate(III)

Summary. Efficient ring opening of epoxides under mild conditions is reported. Potassium dodecatungstocobaltate(III) trihydrate was used as an efficient catalyst for the alcoholysis and acetolysis of epoxides. Conversion of epoxides to thiiranes was also performed efficiently in the presence of this catalyst.     

Dechlorination of chloroethylenes by cob(I)alamin and cobalamin model complexes

Cobalt-mediated dehalogenation reactions, specifically those that employ cobalamin, have attracted particular attention because these complexes rapidly degrade tetrachloroethylene (PCE) and trichloroethylene (TCE), which are common groundwater contaminants. Although questions remain about the relative importance of several pathways, both radicals and organometallic intermediates, specifically chlorovinyl complexes, play an important role in these processes. This Perspective highlights recent studies focused on elucidating the mechanism of chloroethylene degradation, including experimental studies on PCE and TCE dechlorination, computational studies, preparation of model complexes, and the study of model catalytic systems.     

Electrofugal Fragmentation of Alkylcobalamin Derivatives Using Cob(I)Alamin and Heptamethyl Cob (I)yrinate as Catalysts

The cob (I)alamin- ( 1(I) ) and the heptamethyl cob(I)ynnate- ( 2(I) ) catalyzed transformation of an epoxide to the corresponding saturated hydrocarbon 3→4→5 is examined (see Schemes 1 and 3–5). Under the reaction conditions, the epoxyalkyl acetate 3 is opened by the catalysts with formation of appropriate (b?-hydroxyalkyl)-corrinoid derivatives ( 13 , 14 , 17 , 18 , see Schemes 12 and 14). Triggered by a transfer of electrons to the Co-corrin-π system, the Co, C-bond of the intermediates is broken, generating the alkenyl acetate 4 (cf. Schemes 12 and 14) following an electrofugal fragmentation (cf. Schemes 2 and 12). The double bond of 4 is also attacked by the catalysts, leading to the corresponding alkylcorrinoids ( 15 , 19 , see Schemes 12 and 14) which in turn are reduced by electrons from metallic zinc, the electron source in the system, inducing a reductive cleavage of the Co, C-bond with production of the saturated monoacetate 5 (see Schemes 2, 5 and 12). In the cascade of steps involved, the transfer of electrons to the intermediate alkylcorrinoids ( 13–15 , 17–19 , see Schemes 12 and 14) is shown to be rate-limiting. Comparing the two catalytic species 1(I) and 2(I) , it is shown that the ribonucleotide loop protects intermediate alkylcobalamins to some extent from an attack by electrons. The protective function of the ribonucleotide side-chain is shown to be present in alkylcobalamins existing in the base-on form (cf. Chap. 4 and see Scheme 14).