CPAPhosAuCl as Dual Chiral Organocatalyst and Au(I)-Complex for Relay Catalysis: Application in the Synthesis of Chiral Indole Alkaloids

CPAPhosAuCl complexes act as chiral catalysts, embedding two catalytically active moieties: phosphoric acid and a gold metallic center. These complexes are employed sequentially as chiral phosphoric acid organocatalysts and then as cationic Au(I) complexes in the same pot, hence catalyzing two consecutive catalytic cycles with two different catalytic modes. This concept was applied to the formation of chiral polycyclic indole derivatives via enantioselective Pictet-Spengler reactions, followed by ring-closing hydroamination reactions. This protocol was applied to a series of alkyne aldehydes, leading to tetracyclic indolo[2,3-a]quinolizidines and indolo[2,3-a]indolizidines with high enantioselectivities. CPAPhosAuCl allowed control of the 5-exo or 6-endo regioselectivity, depending on the activation strategy to trigger the organometallic reactivity, and promoted an unusual rearrangement that was not observed with classical Au(I) complexes. The strategy was applied to the total synthesis of (+)-cuscutamine.