Synthesis of Enantioenriched 2-Substituted 4-Phenylbutylamines by Hydrogenolysis of Optically Pure 6-Alkoxy-5,6-dihydro-4H-1,2-oxazines
作者:Monika Buchholz、Florian Hiller、Hans-Ulrich Reißig
DOI:10.1002/1099-0690(200208)2002:16<2838::aid-ejoc2838>3.0.co;2-o
日期:2002.8
Lewis acid promoted exchange of the 6-ethoxy group of 6H-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%. (C) Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.