Corrins kinetic formation

Numerous kinetic template reactions have been employed in the formation of porphyrins, corrins and phthalocyanins (see Section 61.1.3). The most instructive examples from a mechanistic point of view are those employed by Eschenmoser and his coworkers in the formation of corrins and... 

Two major mechanisms have to be taken into consideration for the alkylation of Co -corrins. The classical mechanism of a bimolecular nucleophilic substitution reaction at carbon (the Co -corrin acts as a nucleophile) leads to /3-aUcylated Co -corrins with high diastereoselectivity. Secondly, an electron transfer-induced radical process (where the Co -corrin acts as a one-electron reducing agent) may also lead to cobalt alkylation. The observed formation of incomplete a-aUcylated Co -corrins under kinetically controlled conditions has been proposed to occur via this path. The high nucleophilic reactivity of Co -corrins and their diastereoselective nucleophilic reaction on the ( upper ) /3-face are not increased by the nucleotide function on the ( lower ) a-face rather they appear to be an inherent reactivity of the corrin-bound tetracoordinate Co -center. Among the organometallic B12 derivatives prepared to date, neopentylcobalamin, benzylcobalamin, and... 

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 solution the intramolecular coordination of the nucleotide function to the lower a-axial coordination site of the corrin-bound cobalt center of complete corrins occurs with Httle build-up of strain [149]. This allows the (coordinating) nucleotide to steer the reactivity, as well as the face-selectivity, of certain organometalUc reactions involving the corrin-boimd cobalt center [75]. Experiments by Eschenmoser demonstrated that cobal-amins can self-constitute in solution from the Bi2-nucleotide portion and incomplete cobyrinic acid derivatives to show a remarkable kinetic and thermodynamic preference for the specific formation of the B 12-structure, and to a pre-enzymatic origin of the basic structural elements of the complete corrins [149]. 

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