Journal
TETRAHEDRON
Volume 59, Issue 23, Pages 4223-4229Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0040-4020(03)00578-7
Keywords
amino acids and derivatives; stereoselective alkylations; enantioselective protonations; chiral bases; solvent and salt effects
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Achiral 1-benzoyl-3-methylperhydropyrimidin-4-one (1) was deemed a useful, potential precursor for the enantioselective synthesis of alpha-substituted beta-amino acids. Pyrimidinone 1 was prepared from inexpensive beta-aminopropanoic acid in 62% overall yield. Prochiral enolate derivative 1-Li was alkylated in good yield and moderate enantioselectivity in the presence of chiral amines (S)-8, (S,S)-9, (S,S)-10, or (-)-sparteine. The enantioselectivity of the alkylation process is highest in toluene as the solvent and in the presence of lithium bromide as additive. The racemic alkylated derivatives 2 and 3 were readily metallated with LDA to give prochiral enolates 2-Li and 3-Li, that were reprotonated with novel chiral phenolic acids (S)-11, (S,S)-12, (S)-13, and (S,S)-14 in moderate enantioselectivity in the case of 2-Li and good enantioselectivity in the case of 3-Li. The acid (6N HCl) hydrolysis of enantioenriched 2 and 3 proceeded in good yield and without racemization to afford alpha-alkyl-beta-amino acids 4 and 5, respectively. (C) 2003 Published by Elsevier Science Ltd.
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