Premium
Enantiospecific Stereodivergent Synthesis of trans ‐ and cis ‐ N (2),3‐Dimethyl‐4‐phenyl‐1,2,3,4‐tetrahydroisoquinolines
Author(s) -
Coote Steven J.,
Davies Stephen G.,
Fletcher Ai M.,
Roberts Paul M.,
Thomson James E.
Publication year - 2010
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.200900470
Subject(s) - chemistry , tetrahydroisoquinoline , moiety , ephedrine , stereoselectivity , chromium , stereochemistry , isoquinoline , medicinal chemistry , walden inversion , catalysis , organic chemistry , neuroscience , biology
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.