Stereoselective synthesis of perillaldehyde-based chiral β-amino acid derivatives through conjugate addition of lithium amides

Z. Szakonyi, Reijo Sillanpää, F. Fülöp

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10 Citations (Scopus)

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, 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.

Original languageEnglish
Pages (from-to)2738-2742
Number of pages5
JournalBeilstein Journal of Organic Chemistry
Volume10
DOIs
Publication statusPublished - Nov 21 2014

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Lithium
Amides
Esters
Derivatives
Amino Acids
Isomers
Stereoselectivity
Amines
Peptides
perillaldehyde

Keywords

  • Asymmetric synthesis
  • Chiral
  • Michael addition
  • Monoterpene
  • β-amino acid

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

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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, 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.",
keywords = "Asymmetric synthesis, Chiral, Michael addition, Monoterpene, β-amino acid",
author = "Z. Szakonyi and Reijo Sillanp{\"a}{\"a} and F. F{\"u}l{\"o}p",
year = "2014",
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T1 - Stereoselective synthesis of perillaldehyde-based chiral β-amino acid derivatives through conjugate addition of lithium amides

AU - Szakonyi, Z.

AU - Sillanpää, Reijo

AU - Fülöp, F.

PY - 2014/11/21

Y1 - 2014/11/21

N2 - 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, 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.

AB - 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, 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.

KW - Asymmetric synthesis

KW - Chiral

KW - Michael addition

KW - Monoterpene

KW - β-amino acid

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