Syntheses of Tetracyclic Indoline Derivatives Via Gold(I)-Catalyzed Hydroamination/Cycloisomerization Cascade of 2‑Ethynyltryptamides

A gold­(I)-catalyzed hydroamination/cycloisomerization cascade reaction was developed to yield indolizino­[8,7-b]­indole and indolo­[2,3-a]-quinolizine derivatives from 2-ethynyltryptamides. The optimal conditions were determined by condition screening, and the functional group tolerances of these reactions were explored based on synthetic substrates. An insight into the explanation on the selectivity of the ring closure was obtained by density functional theory calculations. A plausible mechanism for the cascade reactions was proposed. Derivatization of the indolizino­[8,7-b]­indole and total synthesis of nauclefidine demonstrated the practicality of this strategy.