An Asymmetric Organocatalytic Povarov Reaction with 2‑Hydroxystyrenes

An organocatalytic asymmetric three-component Povarov
reaction involving 2-hydroxystyrenes has been established to provide
an efficient method to access structurally diverse cis-disubstituted tetrahydroquinolines in high stereoselectivities of
up to >99:1 dr and 97% ee. This
protocol also provides an easy access to tetrahydroquinolines with
chiral quaternary stereocenters upon using α-alkyl 2-hydroxystyrenes
as substrates. The theoretical studies revealed that the Povarov reaction
proceeded through a sequential vinylogous Mannich reaction and an
intramolecular Friedel–Crafts reaction, wherein the phosphoric
acid acted as bifunctional catalyst to activate 2-hydroxystyrene and
aldimine simultaneously.