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Nucleophile Ringöffnung von α‐Nitrocyclopropancarbonsäure‐arylestern mit sterisch geschützter, aber elektronisch wirksamer Carbonyl‐ und Nitro‐Gruppe. Ein neues Prinzip der α‐Aminosäure‐Synthese (2‐Aminobutansäure‐a 4 ‐Synthon)
Author(s) -
Seebach Dieter,
Häner Robert,
Vettiger Thomas
Publication year - 1987
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19870700607
Subject(s) - chemistry , nucleophile , synthon , stereochemistry , substituent , steric effects , medicinal chemistry , aryl , ring (chemistry) , nitro , azide , organic chemistry , catalysis , alkyl
Nucleophilic Ring Opening of Aryl α‐Nitrocyclopropanecarboxylates with Sterically Protected but Electronically Effective Carbonyl and Nitro Group. A New Principle of α‐Amino Acid Synthesis (2‐Aminobutanoic Acid a 4 ‐Synthon) The readily available 2,4,6‐tri( tert ‐butyl)‐and 2,6‐di( tert‐butyl )‐4‐methoxypahenol esters 2 of α‐nitrocyclo‐propanecarboxaylic acid ring opening with C‐, N‐, O‐, and S‐nucleophiles (cyanide, malonate, azide, anilines, alkoxides, phenoxides, thiolates) in DMF or alcohol solvents (80–95% yield). The products 6 – 14 are 2‐nitrobutanoates with the newly introduced substituent in the 4‐position. Reduction of the NO 2 group with Zn/AcOH/Ac 2 O gives N ‐acetyl‐α‐amino acid esters 16 – 22 (40–90% yield). Subsequent oxidative cleavage (H 2 O 2 /HCOOH) of The p ‐methoxy‐phenyl esters 18 and 20 produces free amino acids (65% 23 and 67% 24 , respectively). Thus, the nitro ester 2 corresponds to a 2‐aminobutanoic‐acid a 4 ‐synthon, it is a ‘homo‐ Michael acceptor’ producing γ‐substituted α‐amino acids.