Total Synthesis of (+)-Eburnamonine Using Asymmetric Alkene Cyanoamidation through C-CN Bond Activation.

We report the total synthesis of (+)-eburnamonine using enantioselective alkene cyanoamidation to form the all-carbon quaternary stereocenter. Palladium, phosphoramidite ligand, and a Lewis acid combine to form a co-catalyst that promotes C-CN activation of a cyanoformamide, followed by intramolecular alkene cyanoamidation. Overall, the synthesis of (+)-eburnamonine is accomplished in 8 steps from 4-methylene hexanoic acid and tryptamine, providing an example of asymmetric aliphatic-tethered alkene cyanoamidation and its use in total synthesis.