Synthesis of Chiral 1-Substituted Tetrahydroisoquinolines by the Intramolecular 1,3-Chirality Transfer Reaction Catalyzed by Bi(OTf)3

The intramolecular 1,3-chirality transfer reaction of chiral amino alcohols 1 with 99% ee was developed to construct chiral 1-substituted tetrahydroisoquinoline 2. Bi(OTf)(3) (10 mol%)-catalyzed cyclization of 1 (R=H) afforded (S)-1-(E)-propenyl tetrahydroisoquinoline 2 (R=H) in 83% yield with a ratio of 98:2. The stereochemistry at the newly formed chiral center was produced by a syn S(N)2'-type process. In this reaction, the substituent on the benzene ring of 1 significantly affected the reactivities and selectivities. A plausible reaction mechanism was proposed.