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.