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Synthesis 2002(5): 0625-0630
DOI: 10.1055/s-2002-23537
PAPER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Enantiomerically Pure 8-Substituted 5,6,7,8-Tetrahydroquinolines

Junichi Uenishi*, Masahiro Hamada
Kyoto Pharmaceutical University, Misasagi-Shichonocho, Yamashina Kyoto 607-8412, Japan
Fax: +81(75)5954763; e-Mail: juenishi@mb.kyoto-phu.ac.jp;
Further Information

Publication History

Received 25 December 2001
Publication Date:
02 April 2002 (online)

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Abstract

Enantiomerically pure (S)-5,6,7,8-tetrahydroquinolin-8-ol [(S)-1] and (R)-8-acetoxy-5,6,7,8-tetrahydroquinoline [(R)-2] have been prepared by the lipase-catalyzed kinetic acetylation of racemic 5,6,7,8-tetrahydroquinolin-8-ol [(±)-1] in excellent chemical yields. The mesylation of (R)-1 followed by a substitution reaction with the azide, thioacetate, and dimethyl malonate anions and benzylamine gives the corresponding substituted products in an enantiomerically pure form with an inversion of the configuration in good yields. The methanolysis of (S)-5,6,7,8-tetrahydroquinolin-8-yl acetate in the presence of potassium carbonate and alkylation of the resulting thiol anion with alkyl halides in a one-pot reaction gives the 5,6,7,8-tetrahydroquinolin-8-yl thioether.

Key words

8-substituted quinolines - enzymatic acetylation - nucleophiles - stereospecific substitutions - asymmetric synthesis

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The details including the columns and conditions are described in the experimental section.

14

(R)-Alcohol was specifically acetylated under the conditions, and no exception has ever been observed so far at least using Candida antarctica lipase.