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.