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Synthesis of Enantioenriched 2‐Substituted 4‐Phenylbutylamines by Hydrogenolysis of Optically Pure 6‐Alkoxy‐5,6‐dihydro‐4 H ‐1,2‐oxazines
Author(s) -
Buchholz Monika,
Hiller Florian,
Reißig HansUlrich
Publication year - 2002
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200208)2002:16<2838::aid-ejoc2838>3.0.co;2-o
Subject(s) - hydrogenolysis , chemistry , enantiopure drug , diastereomer , oxazines , alkoxy group , amine gas treating , organic chemistry , enantiomer , medicinal chemistry , stereochemistry , catalysis , enantioselective synthesis , alkyl
Lewis acid promoted exchange of the 6‐ethoxy group of 6 H ‐1,2‐oxazines 1−3 with (−)‐menthol furnished the optically active heterocycles 4 − 6 . Diastereomers 4a and 4b , which could be separated efficiently by chromatography, were excellent substrates for highly diastereoselective conjugate additions of phenyllithium and n ‐butyllithium, thus providing the enantiopure trans ‐substituted 1,2‐oxazines 7a , 7b , 8a , and 8b in good yields. Exhaustive hydrogenolysis of 7a afforded the primary amine 9 with an enantiomeric excess of 80%, whereas hydrogenolysis of 8a and 8b gave the corresponding amines ( R )‐ 11 and ( S )‐ 11 , respectively, with an ee of more than 90%. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)