Enantiospecific stereodivergent synthesis of trans- and cis-N(2),3-dimethyl-4-phenyl-1,2,3,4-tetrahydroisoquinolines.

Journal article

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.

Authors: Coote, S; Davies, S; Fletcher, A; Roberts, P; Thomson, J

• Publication status: Published
• Journal: Chemistry, an Asian journal
• Volume: 5
• Issue: 3
• Pages: 589-604
• Publication date: 2010-03-01
• DOI: 10.1002/asia.200900470
• EISSN: 1861-471X
• ISSN: 1861-4728
• Language: English
• Keywords: Ephedrine; Cyclization; Stereoisomerism; Isoquinolines; Ethanolamines