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

Article abstract of DOI:10.1002/asia.200900470

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. Acidpromoted 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.