Efficient and Chirally Specific Synthesis of Phenanthro-Indolizidine Alkaloids by Parham-Type Cycloacylation

A concise, efficient and modular route involving Parham-type cycloacylation as the key step has been used to synthesize six enantiopure phenanthro-indolizidine alkaloids 1a-c. The preparation of enantiomerically pure tylophora alkaloids and their seco analogues on a large-scale is now feasible. The alcohol intermediates 8a-c, which are difficult to prepare by other synthetic methodologies, have been synthesized by a metallation-cyclization-reduction sequence in excellent yields.