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Application of the Chelate‐Enolate Claisen Rearrangement to The Synthesis of γ,δ‐Unsaturated Amino Acids
Author(s) -
Kazmaier Uli
Publication year - 1997
Publication title -
liebigs annalen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0947-3440
DOI - 10.1002/jlac.199719970203
Subject(s) - chemistry , chelation , chirality (physics) , allylic rearrangement , deprotonation , amino acid , moiety , asymmetric carbon , stereochemistry , enantioselective synthesis , denticity , medicinal chemistry , metal , organic chemistry , catalysis , alkyl , ion , biochemistry , chiral symmetry breaking , physics , quantum mechanics , nambu–jona lasinio model , quark
Deprotonation of N ‐protected amino acid allylic esters with LDA at −78°C and subsequent addition of a metal salt presumably results in the formation of a chelated metal enolate that undergoes Claisen rearrangement upon warming up to room temperature, giving rise to γ,δ ‐unsaturated amino acids. Many different metal salts can be used for chelation, but in general the best results are obtained with zinc chloride. Due to the fixed enolate geometry, as a result of chelate formation, and a strong preference for the chair‐like transition state, the rearrangement proceeds with a high degree of diastereoselectivity. This method can be applied to acyclic as well as to cyclic substrates, and even to peptides, and allows the synthesis of amino acids containing quaternary carbon centers. Esters of chiral allylic alcohols produce optically active amino acids via chirality transfer from the ester moiety to the α‐carbon center of the amino acid. Another possibility to introduce chirality is given by the rearrangement in the presence of chiral ligands. The best results are obtained if Al(O i Pr) 3 is used as the chelating metal salt and the Chinchona alkaloids as bidentate ligands. Quinine gives rise to (2 R )‐configured amino acids, whereas quinidine delivers the (2 S ) derivatives in very high yields and excellent enantioselectivities (80–93% ee). The ligands can easily be recovered nearly quantitatively from the reaction mixture.