Synthesis 2003(2): 0251-0254
DOI: 10.1055/s-2003-36832
PAPER
© Georg Thieme Verlag Stuttgart · New York

Resolution of 1-Aryl-1,2,3,4-Tetrahydroisoquinolines via Crystallization of O-Acetylmandelic Amides

Edgars Suna*
Latvian Institute of Organic Synthesis, Riga, 1006, Latvia
Fax: +371(7)553142; e-Mail: edgars@osi.lv;
Further Information

Publication History

Received 26 September 2002
Publication Date:
22 January 2003 (online)

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Abstract

(R)-O-Acetylmandelic acid is an efficient chiral auxiliary for the resolution of racemic 1-aryl-1,2,3,4-tetrahydroisoquinolines 2 and 3 via crystallization of the corresponding diastereomeric amides 5 and 7. Acidic hydrolysis of (R,S)-O-acetylmandelylanilide 7b afforded optically pure (>99% ee) (S)-1-(2-aminophenyl)-1,2,3,4-tetrahydroisoquinoline (3b). Removal of the chiral auxiliary attached to the tetrahydroisoquinoline nitrogen (amide 5a) afforded partially racemized amine 2 both under hydrolytic and reductive cleavage conditions. Brønsted acid catalyzes migration of the chiral auxiliary from the isoquinoline nitrogen to aniline (6a7a).