Asymmetric Three-Component Reaction to Assemble the Acyclic All-Carbon Quaternary Stereocenter via Visible Light and Phosphoric Acid Catalysis

Chiral acyclic all-carbon quaternary stereocenters are
widely present
in natural products and pharmaceuticals. However, their introduction
remains a challenging topic in the synthetic research community. Here,
we report an efficient metal-free method for the construction of acyclic
all-carbon quaternary chiral centers sited at the α-position
of an aldehyde or ketone moiety. This is achieved via a well-designed
reaction cascade involving arylalkynes, benzoquinones, and electron-rich
(hetero)­arenes and the use of visible light and phosphoric acid catalysis.
Notably, the asymmetric catalytic visible-light-induced Paternò–Büchi
cycloaddition/electrocyclic ring-opening/α-selective arylation
of α,β-unsaturated carbonyl compound cascades is achieved.
Moreover, the reaction works well for a broad range of these three
components (>70 examples). Furthermore, the rich chemistry embedded
in the products provides a variety of synthetically useful building
blocks that are otherwise difficult to access. Lastly, the origin
of enantioselectivity was investigated by density functional theory,
revealing that CH/π interactions play a crucial role in the
stereocontrol of the reaction.