Homolytic macrocyclization

Synthesis of 12- and 13-membered sulfur-containing lactones by homolytic macrocyclization of mercaptoacetic esters and alkynes has been investigated [95S307]. Reaction of the mercaptoester 245 with alkynes using triethyl borane radical initiation gave the macrolactones 247 and 248 in low yield [95TL2293], Remote asymmetric induction is observed during the cyclization. 

Under appropriate circumstances, free-radical methods can also be used to prepare macrocyclic systems. For example, Maillard and coworkers prepared the 12-membered macrocyclic ether (102) by Bu3SnH-mediated intramolecular homolytic addition to a remote, but activated (a, / unsaturated) olefin as depicted in equation 77460. Tozer and coworkers employed 7-, 8- and 9-endo cyclization in their preparations of conformationally constrained amino acids (103), an example of which is provided in equation 78448. 

Photo-homolytic cleavage of Co—C bonds has been studied for Vitamin 812 and cobalt(m) complexes with tetra-aza-14-membered macrocyclic ligands. In the latter study, the rate of recombination of the radical with cobalt(ii) is ca. 10 M s at 25 °C. The cobalt(iii) complexes have a low energy threshold to photolysis, >540nm. 

Two examples have been described of the formation of transient dimethylcobalt(IV) macrocyclic complexes, Me2Co(IV)[N4], by electrochemical oxidation of the corresponding cobalt(III) compound. These decompose to a monomethylcobalt(III) species and ethane deuterium labeling and radical-trapping experiments show that the process involves homolytic Co-C bond fission as in (43). There is thus a formal similarity to reaction (14). ... 

A Swiss group has reported on a new fragmentation mode of bicyclic enol ethers, when macrocyclic lactones are obtained vicinal a-hydroperoxytetra-hydropyranyl ethers (33) annelated to cyclododecane, prepared via the corresponding cyclododecanone enol ethers, are smoothly converted homolytically into a mixture of macrocyclic lactones. This fragmentation has been developed to provide an economically feasible synthesis of exaltolide (34). 

The stability constants for the coordination of pyridine or substituted pyridines to various alkylcobalt porphyrin systems have been reported. This study has been done in order to observe the m-influence of hydroporphyrin macrocycles on axial position and alkyl exchange reactions. The alkyl exchange reactions of organocobalt(lll) porphyrins with a cobalt(ll) complex of a distinguishable porphyrin or tetrapyrrolc have been studied. The equilibrium constants for the alkyl transfer have been reported. The exchange of the axial ligand is reversible and it follows a bimolecular mechanism. Thermodynamic and activation parameters for homolytic Co-C bond dissociation have been obtained on the (TAP)CoC(CH3)2CN complex (TAP = tetraanisylporphirinato). ... 

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