Highly Enantioselective Tandem Michael Addition of Tryptamine-Derived Oxindoles to Alkynones: Concise Synthesis of Strychnos Alkaloids

A highly enantioselective tandem Michael addition of tryptamine-derived oxindoles to alkynones was developed by taking advantage of a chiral N,N-dioxide Sc(OTf)(3) catalyst. The reaction enables the facile preparation of enantioenriched spiro[pyrrolidine-3,3-oxindole] compounds, which provides a novel strategy for the synthesis of monoterpenoid indole alkaloids. As a demonstration, the asymmetric synthesis of strychnos alkaloids [(-)-tubifoline, (-)-tubifolidine, (-)-dehydrotubifoline] was achieved in 10-11 steps.