Multiple Hydrogen-Bond Activation in Asymmetric Brønsted Acid Catalysis.

An efficient protocol for the asymmetric synthesis of chiral tetrahydroquinolines bearing multiple stereogenic centers by means of asymmetric Brønsted acid catalysis was developed. A chiral 1,1'-spirobiindane-7,7'-diol (SPINOL)-based N-triflylphosphoramide (NTPA) proved to be an effective Brønsted acid catalyst for the in situ generation of aza-ortho-quinone methides (aza-o-QMs) and their subsequent cycloaddition reaction with unactivated alkenes to provide the products with excellent diastereo- and enantioselectivities. In addition, DFT calculations provided insight into the activation mode and nature of the interactions between the N-triflylphosphoramide catalyst and the generated aza-o-QMs.