Total Synthesis of Phenanthroindolizidines Using Strained Azacyclic Alkynes

Wereport a concise approach to phenanthroindolizidine alkaloids,wherein strained azacyclic alkynes are intercepted in Pd-catalyzedannulations. Two types of strained intermediates were evaluated: afunctionalized piperidyne and a new strained intermediate, an indolizidyne.We show that each can be employed, ultimately allowing access to threenatural products: tylophorine, tylocrebine, and isotylocrebine. Theseefforts demonstrate the successful merger of strained azacyclic alkynechemistry with transition-metal catalysis for the construction ofcomplex heterocycles.

Automated summary

We report a concise approach to the synthesis of phenanthroindolizidine alkaloids, utilizing the interception of strained azacyclic alkynes in Pd-catalyzed reactions. Two types of strained intermediates, a functionalized piperidyne and a new strained intermediate, indolizidyne, were evaluated. These efforts resulted in the successful synthesis of three natural products: tylophorine, tylocrebine, and isotylocrebine, demonstrating the successful combination of strained azacyclic alkyne chemistry with transition-metal catalysis for the construction of complex heterocycles.