Formation of the Co—C Bond

The Co—C bond can be formed by reactions of the following main types  

Co(I) or Co—H complexes + electrophiles (e.g. CH3I, HC CH, olefins) Co(II) complexes + radicals (and possibly electrophiles) 

In this section we concentrate on the types of reaction, their kinetics, stereochemistry, and mechanism, and deal with the above groups in turn Section IV deals with the practical details of applying these and other reactions to the synthesis of organocobalt(III) complexes. 

The simple Co(I) complexes may reversibly pick up a proton to give what is essentially a Co(III) complex with a coordinated hydride, i.e., 

These complexes can react with a wide range of electrophilic reagents, which can be classified roughly into the following groups [equations are written only for Co(I) complexes]. 

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Reaction of alkyl Grignard and other organometallic reagents with Co(III) species was originally used for formation of the Co—C bond , in particular for the preparation of alkylcobalamin analogues . 

In solution cleavage and formation of the Co - C bond have been observed to occur in all of the basic oxidation levels for the cobalt center of the corrin core [115-118]. Two main paths for these organometallic reactions have been found ... 

For the homolytic mode of formation of the Co - C bond in coenzyme Bi2 (2) the structure [51] and reactivity of cob(II)alamin (23) gave crucial information. The radicaloid 23 has a pentacoordinated Co(II) center and is considered to fulfill all the structural criteria of a highly efficient radical trap (see Fig. 10), since its reactions with alkyl radicals occur with negligible restructuring of the DMB-nucleotide coordinated cobalt-corrin moiety [51]. From this it is understandable that the remarkably high reaction rate of 23 with alkyl radicals (such as the 5 -deoxy-5 -adenosyl radical) and the diastere-ospecificity for the reaction to occur at the j8-face, are both consistent and explainable due to the structure of cob(II)alamin. The coordination of the DMB-nucleotide in 23 controls the (a/j8)-diastereoface selectivity (in both a kinetic and thermodynamic sense) in alkylation reactions at the Co(II) center. 

The stereochemical situation however, is appreciably more complex in incomplete corrins, such as cob(II)ester (24) and base-off forms of complete corrins. The axial ligand at the corrin-boimd Co(II) center is expected to direct the formation of the Co - C bond. In this way kinetic control can lead with high efficiency to the rare Q -alkyl-Co(III)-corrins [84,128[. In such radical recombination reactions the axial ligand at the a- or -side of the metal center will not only steer the diastereoselectivity of the alkylation but also may contribute to significant altering of the cage effects [122,123[. 

In the heterolytic mode of cleavage and formation of the Co - C bond significant reorganization at both faces of the corrin-bound cobalt center. Cleavage of the Co - CH3 bond is brought about by attack of a nucleophile at the readily accessible carbon of the cobalt-bound methyl group. 

A crystal structure of the C02 derivative of (8), K[Co(salen)( 71-C02)], haso been reported in which the Co—C bond is 1.99 A, the C—O bonds are both equivalent at 1.22 A and the O-C-O angle is 132°.125 Carboxylation of benzylic and allylic chlorides with C02 in THF-HMPA was achieved with (8) electrogenerated by controlled-potential electrolysis,126 in addition to reductive coupling of methyl pyruvate, diethyl ketomalonate and / -tolylcarbodiimide via C—C bond formation. Methyl pyruvate is transformed into diastereomeric tartrates concomitant with oxidation to the divalent Co(salen) and a free-radical mechanism is proposed involving the homolytic cleavage of the Co—C bond. However, reaction with diphenylketene (DPK) suggests an alternative pathway for the reductive coupling of C02-like compounds. 

From these data it seems feasible that a Co(II)-species is generated during catalysis, and that homolysis of the Co—C-bond is a prerequisite for enzyme catalysis in ribonucleotide reductase. However, the kinetics of appearance of the Co(II)-signal indicates that the rate of formation of Co(II) is much slower than either the rate of ribonucleotide reduction... 

Metal-centred corrinoid chemistry is represented by the chemistry of the Co—C bond . The reactions which lead to Co—C bond formation are summarized in Scheme 100.271... 

As will be noted later, it is commonly thought that homolytic cleavage of the Co—C bond is an important initial stage in the reactions of cobalamins. Accordingly, there has been much interest in the formation of Co—C bonds, the factors that determine their stability, and the cleavage of these Co—C bonds. 

Thermochemical. Application to the estimation of the enthalpy of a process such as that depicted by Equation 15 requires determination of the heats of formation of LnM—R, R , and LnM . The latter usually is not accessible to measurement although it is in the case of alkyl-cobalamins (where LnM- corresponds to vitamin B12r, a stable and accessible compound). Thus, thermochemical approaches, in principle, are potentially applicable to the estimation of the Co-C bond dissociation energy in coenzyme B12. However, the practical difficulties are considerable and the probable accuracy of the result is questionable. 

The reaction of a Co(I) nucleophile with an appropriate alkyl donor is used most frequently for the formation of a Co-C bond, which also can be formed readily by addition of a Co(I) complex to an acetylenic compound or an electron-deficient olefin (5). The nu-cleophilicity of Co(I) in Co(I)(BDHC) is expected to be similar to that in the corrinoid complex, as indicated by their redox potentials. The formation of Co-C a-bond is the attractive criterion for vitamin Bi2 models. Sodium hydroborate (NaBH4) was used for the reduction of Co(III)(CN)2(BDHC) in tetrahydrofuran-water (1 1 or 2 1 v/v). The univalent cobalt complex thus obtained, Co(I)(BDHC), was converted readily to an organometallic derivative in which the axial position of cobalt was alkylated on treatment with an alkyl iodide or bromide. As expected for organo-cobalt derivatives, the resulting alkylated complexes were photolabile (17). 

Alkylated cobaloximes yield the corresponding dimeric species of alkyl radicals by photolysis under acidic conditions. But the BDHC complex with a hexyl or benzyl group at its axial site does not yield the corresponding dimeric species by photolysis (dodecane and bibenzyl, respectively). Consequently, the hydrogenation product must be obtained through the formation of a carbanion by heterolytic cleavage of the Co-C bond, followed by its protonation. 

Cleavage of the Co-C bond to the deoxyadenosyl group, with the probable formation of a 5 -deoxyadenosyl radical. 

The polymer binding of low molecular N202-chelates like Co(salen) (6) starts from its monoanion and poly(chloromethylstyrene) in THF at 193 K. The high reactivity erf the reduced (6) leads to the polymer (61) by formation of a Co-C bond in 100% yield. But no use of such an easily accessible polymer is yet known. 

The main evidence is that the values of kc for the small radicals obtained with the CCT-based method are very close to those obtained by other methods.55 65 This is not to say that formation of a Co—C bond does not occur it is simply not an important step on the catalytic cycle.66 It does, however, remove catalyst from the catalytic cycle. 

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