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.
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK.
Steven J
SJ
Coote
Stephen G
SG
Davies
Ai M
AM
Fletcher
Paul M
PM
Roberts
James E
JE
Thomson
D003500:Cyclization; D004809:Ephedrine / Q000737:chemistry; D004983:Ethanolamines / Q000737:chemistry; D007546:Isoquinolines / Q000138:chemical synthesis*; D013237:Stereoisomerism
D004983:Ethanolamines; D007546:Isoquinolines; D004809:Ephedrine