Enantiospecific Stereodivergent Synthesis of trans- and cis-N(2),3-Dimethyl-4-phenyl-1,2,3,4-tetrahydroisoquinolines

The acid‐promoted cyclizations of a range of N‐benzylethanolamines (derived from pseudoephedrine or ephedrine) give the corresponding trans‐N(2),3‐dimethyl‐4‐phenyl‐1,2,3,4‐tetrahydroisoquinolines with high levels of diastereoselectivity and in good yields of isolated product. The cyclizations of the corresponding chromium tricarbonyl complexes are rendered completely stereoselective. Acid‐promoted cyclization of N‐(3′,4′‐dimethoxybenzyl)ephedrine and its chromium tricarbonyl complex occur with complementary diastereoselectivities to give trans‐ and cis‐N(2),3‐dimethyl‐4‐phenyl‐6,7‐dimethoxy‐1,2,3,4‐tetrahydro‐isoquinoline, respectively, in >99:1 d.r. The latter is consistent with a “double inversion” mechanism, which involves neighboring group participation by the chromium tricarbonyl moiety followed by rearomatization to give the corresponding cis‐tetrahydroisoquinoline with overall retention of configuration. Tetrahydroisoquinoline synthesis: Acid‐promoted cyclization of 1,2‐disubstituted N‐benzylethanolamines or their chromium tricarbonyl complexes (derived from ephedrine or pseudoephedrine) gives trans‐ or cis‐N(2),3‐dimethyl‐4‐phenyl‐1,2,3,4‐tetrahydroisoquinolines in high d.r.