The <i>Aspidosperma</i> alkaloid (+)–eburnamonine is a relevant target for enantioselective total synthesis due to its potency as a cerebral vasodilator and anti-tumor drug. We have proposed an efficient, 11-step, enantioselective synthesis of (+)–eburnamonine. We present our synthetic pathway that features reactions with reproducible yields and relatively mild conditions. Our synthesis highlights a palladium-catalyzed asymmetric cyanoamidation reaction, which intramolecularly forms a lactam with an all-carbon quaternary stereocenter by C–CN bond activation. The synthesis of the cyanoamidation starting material features a CuI-catalyzed carbometalation of propargyl alcohol, a Johnson-Claisen rearrangement, carbonyl diimidazole (CDI) coupling with tryptamine, lithium aluminum hydride (LAH) reduction, and cyanoformylation of the resulting secondary amine by in situ preparation of carbonyl cyanide from tetracyanoethylene oxide (TCEO) and dimethyl sulfide.

Total synthesis of (+)–eburnamonine through a Pd-catalyzed asymmetric cyanoamidation reaction

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