Synthesis of enantioenriched 2-substituted 4-phenylbutylamines by hydrogenolysis of optically pure 6-alkoxy-5,6-dihydro-4H-1,2-oxazines

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.