title: Stereoselective synthesis of perillaldehyde-based chiral β-amino acid derivatives through conjugate addition of lithium amides.
abstract: The Michael addition of dibenzylamine to (+)-tert-butyl perillate (3) and to (+)-tert-butyl phellandrate (6), derived from (S)-(-)-perillaldehyde (1), resulted in diastereomeric β-amino esters 7A-D in a moderately stereospecific reaction in a ratio of 76:17:6:1. After separation of the diastereoisomers, the major product, cis isomer 7A, was quantitatively isomerized to the minor component, trans-amino ester 7D. All four isomers were transformed to the corresponding β-amino acids 10A-D, which are promising building blocks for the synthesis of β-peptides and 1,3-heterocycles in three steps. The steric effects of the isopropyl group at position 4 and of the α-methyl substituent of (R)-N-benzyl-N-α-methylbenzylamine on the reactivity were also studied and, upon application of a chiral amine, excellent stereoselectivity of the conjugate addition was observed. Amino ester 11 was obtained as a single product and transformed to the corresponding amino acids 10A and 10D in good yields on the gram scale.
authors.affiliation: Institute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Eötvös utca 6, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szakonyi
authors.affiliation: Department of Chemistry, University of Jyväskylä, POB 35, 40351 Jyväskylä, Finland.
authors.forename: Reijo
authors.initials: R
authors.lastname: Sillanpää
authors.affiliation: Institute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Eötvös utca 6, Hungary ; Stereochemistry Research Group of the Hungarian Academy of Sciences, H-6720 Szeged, Eötvös u. 6, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Fülöp
keywords: Michael addition; asymmetric synthesis; chiral; monoterpene; β-amino acid