Total Synthesis of Phenanthroindolizidines Using Strained Azacyclic Alkynes

We report a concise approach to phenanthroindolizidine alkaloids, wherein strained azacyclic alkynes are intercepted in Pd-catalyzed annulations. Two types of strained intermediates were evaluated: a functionalized piperidyne and a new strained intermediate, an indolizidyne. We show that each can be employed, ultimately allowing access to three natural products: tylophorine, tylocrebine, and isotylocrebine. These efforts demonstrate the successful merger of strained azacyclic alkyne chemistry with transition-metal catalysis for the construction of complex heterocycles.