Multiple Hydrogen-Bond Activation in Asymmetric BrOnsted Acid Catalysis

An efficient protocol for the asymmetric synthesis of chiral tetrahydroquinolines bearing multiple stereogenic centers by means of asymmetric BrOnsted acid catalysis was developed. A chiral 1,1-spirobiindane-7,7-diol (SPINOL)-based N-triflylphosphoramide (NTPA) proved to be an effective BrOnsted acid catalyst for the insitu 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.