Stereodifferentiation in a Chiral 1,4-Oxazin-2-one Derived from 2-Hydroxy-2-methyl-1-tetralone − A Reagent for Deracemization of Amino Acids

Abstract

Non-activated iodides (MeI, EtI, iPrI) provide moderate to good levels of conversion (55−100%) of 1,4-oxazin-2-one (1) into monoalkylated 3-alkyl-1,4-oxazin-2-ones 5, with satisfactory diastereoselectivities (89:11 to 92:8) and reasonably low amounts of dialkylation (0 to 36%). Alkylation of 3-methyl-1,4-oxazin-2-one (5a) occurs with high levels of conversion (82 to 100%), total diastereoselectivity, and only a small amount of O-alkylation, thus providing a three-step synthesis of enantiopure quaternary amino acids. Enantiopure (R)- or (S)-2-hydroxy-2-methyl-1-tetralone (4) can be efficiently used to epimerize/deracemize amino acids (with recovery of the excess amino acid used and also of 4, which can be reused). (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)