Cooperative Catalysis-Enabled Asymmetric α‑Arylation of Aldehydes Using 2‑Indolylmethanols as Arylation Reagents

A catalytic
asymmetric α-arylation of aldehydes using 2-indolylmethanols
as arylation reagents has been established. This reaction was enabled
by a cooperative catalytic system consisting of a gold complex, a
Brønsted acid, and a chiral amine, which have a synergistic effect
in the reaction process. By using this strategy, a series of α-arylation
products of aldehydes were generated in overall acceptable yields
and good enantioselectivities (up to 69%, 91:9 er). The control experiments
demonstrated that the addition of PPh3AuCl as a gold complex
was helpful to improve the yield, and trifluoroacetic acid as a Brønsted
acid played a crucial role in the reaction by promoting the generation
of carbocation and chiral enamine intermediates, which are two key
intermediates of the asymmetric α-arylation reaction. In addition,
the enantioselectivity of the reaction was mainly controlled by the
chiral amine catalyst via forming a chiral enamine intermediate. This
reaction has not only provided a useful protocol for catalytic asymmetric
α-arylation of aldehydes but also enriched the research contents
of 2-indolylmethanol-involved reactions and asymmetric cooperative
catalysis.