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Diastereo‐ and Enantioselective Synthesis of Carbocyclic and Heterocyclic β‐Amino Acids by Tandem Aza Michael Addition/Intramolecular Cyclization
Author(s) -
Enders Dieter,
Wiedemann Jürgen
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.199719970410
Subject(s) - chemistry , intramolecular force , moiety , stereoselectivity , enantioselective synthesis , alkylation , stereochemistry , pyrrolidine , conjugate , michael reaction , enantiomer , chiral auxiliary , organic chemistry , catalysis , mathematical analysis , mathematics
The stereoselective conjugate addition of ( S )‐(–)‐1‐(trimethylsilylamino)‐2‐(methoxymethyl)pyrrolidine (TMS‐SAMP) to ω‐halide‐substituted α,β‐unsaturated esters 1 is utilized to prepare carbocyclic and heterocyclic β‐amino acids 2 and 5 of high diastereo‐ and enantiomeric purity via the corresponding β‐hydrazino esters by selective intramolecular alkylation of the intermediate ester enolate or the hydrazino moiety. The auxiliary is removed by reductive NN bond cleavage. The stereochemistry of the resulting trans ‐2‐aminocycloalkanecarboxylic acids ( 2 ) and azacycloalk‐2‐ylacetic acid esters ( 5 ) is confirmed by NMR spectroscopy and polarimetry. A transition‐state model for the highly diastereoselective conjugate addition of TMS‐SAMP to enoates is presented.