Investigation of Mn(III)-based oxidative free radical cyclization reactions toward the synthesis of triptolide: The effects of lanthanide triflates and substituents on stereoselectivity

Mn(III)-mediated oxidative free radical cyclization reactions are useful for construction of polycyclic compounds. In the total synthesis of triptolide (3) and its related compounds, construction of tricyclic skeletons 4 and 5 was achieved by the Mn(OAc)(3)-mediated oxidative radical cyclization of a series of acyclic precursors 6-9. The addition of a catalytic amount of lanthanide triflates was found to significantly improve the rate and stereoselectivity of those radical cyclization reactions. The effects of the benzylic oxygen substituents and alpha-substituents (chloro and methyl) on the radical cyclization reactions were also investigated. Transition-state models were proposed to explain the observed stereoselectivity.