Ligand, Solvent, and Deuterium Isotope Effects in Mn(III)-Based Oxidative Free-Radical Cyclizations

Article abstract of DOI:10.1021/jo00075a015

Oxidation of β-keto ester 1 with Mn(pic)3 and Cu(OAc)2 affords bicycloalkane 8, not the expected alkene 7, which is formed in high yield with Mn(OAc)3 and Cu(OAc)2.A series of control experiments established that the most likely explanation for this observation is that Mn(pic)2, but not Mn(OAc)2, reacts with the bicyclic radical 5 more rapidly than Cu(OAc)2 does.These studies also indicate the potential for improved yields from oxidative free-radical cyclization of deuterated substrates.For instance, reaction of β-keto ester 1-d with 2 equiv of Mn(OAc)3 and no Cu(OAc)2 affords 65percent of 8, whereas β-keto ester 1 provides only 22percent of 8 under the same conditions.Large kinetic isotope effects change the nature of the termination step and prevent the formation of acyclic radical 3 by intermolecular hydrogen transfer.Solvent and ligand effects on the oxidation of β-keto ester 1, malonate 14, and acetylenic β-keto ester 25 are described.