Manganese(III)-based oxidative free-radical polycyclizations

Over the last twenty years, the development of free-radical cyclizations for use in synthesis has undergone a renaissance. However, most of the techniques developed towards this end suffer from the drawback that the cyclizations are initiated and terminated reductively, limiting functionality in the product. The goal of our work has been the development of manganese(III) based oxidative free-radical cyclizations. Manganese(III) cyclizations are initiated and terminated oxidatively, which provides more highly functionalized products.;This work represents our development of manganese(III) based polycyclizations. Oxidation of ;Oxidative free-radical triple cyclizations proceed in good yields. Oxidative cyclization of ;We have studied the scope and limitations of Mn(III) based oxidative cyclizations. We have shown that oxidative-cyclizations proceed via oxidation of the Mn(III) E-enol to give the E-enol radical. The first cyclization takes place through a chair transition state in which the substituents on the tether between the radical and the alkene occupy equatorial positions. The regiochemistry of the first cyclization is influenced by substituents on the alkene.;We have carried out a comparison study of Mn(III) oxidative cyclizations and atom transfer cyclizations in conjunction with Professor Dennis Curran at the University of Pittsburgh. Our results indicate that the initially formed enol radical in a manganese(III) cyclization is a free radical and is not influenced in any way by Mn(III), and that the observed stereo and regioselectivities are due to the nature of the radical.