NHC-Catalyzed Enantioselective [4+3] Cycloaddition of Ortho-Hydroxyphenyl Substituted Para-Quinone Methides with Isatin-Derived Enals

The first enantioselective cycloaddition of ortho-hydroxyphenyl substituted para-quinone methides has been established by employing isatin-derived enals as suitable 3C-synthons under chiral N-heterocyclic carbene catalysis. By using this strategy, biologically important E-lactones have been prepared in good yields (up to 89%) and excellent asymmetric inductions (up to >99%ee, >20:1dr). Notably, this methodology opens a direct [4+3] annulation entry for the asymmetric synthesis of spirobenzoxopinones bearing an oxindole moiety connected through the spirocenter.