Synthesis of tylocrebrine and related phenanthroindolizidines by VOF3-mediated oxidative aryl-alkene coupling

A highly convergent strategy to prepare phenanthroindolizidines is reported involving three consecutive C-C coupling reactions. This sequence features a novel VOF(3)-mediated aryl-alkene coupling in the final step, which enables regioselective preparation of C5-substituted phenanthroindolizidines for the first time. This strategy has been applied to the synthesis of eight natural and unnatural members in this class to investigate the scope of this chemistry and to explore structure-activity relationships.