Fine Tuning Reactivity: Synthesis and Isolation of 1,2,3,12b-Tetrahydroimidazo[1,2-<i>f</i>]phenanthridines

A facile route for the synthesis and isolation of 1,2,3,12b-tetrahydroimidazo[1,2-f]phenanthridines (TIPs) has been developed. The heterocycle is a reactive intermediate in the three-step cascade synthesis of 2,3-dihydro-1H-imidazo[1,2-f]phenanthridinium cations (DIPs), a biologically active DNA intercalating framework; however, the intermediate has previously only been characterized in situ. Derivatization of the structure at the imidazo-N position controls the reactivity of the intermediate with respect to electronic potential and pKa allowing isolation of a selection of TIP structures. Correlations between these parameters and reaction outcome have been made, and other influences such as steric and solvent effects have also been investigated.