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Preparation of α,α‐Disubstituted α‐Amino Acid Derivatives via Alkyl Addition to α‐Oxime Esters with Organozinc Species
Author(s) -
Mitani Michiharu,
Tanaka Yasunori,
Sawada Akihiko,
Misu Ayuko,
Matsumoto Yoshihiro
Publication year - 2008
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200700929
Subject(s) - chemistry , oxime , hydrogenolysis , hydroxylamine , medicinal chemistry , alkyl , isoxazole , alkylation , intramolecular force , catalysis , derivative (finance) , organic chemistry , adduct , financial economics , economics
An α‐oxime ester derivative prepared via treatment of an acetylenedicarboxylate or an α‐keto ester with hydroxylamine underwent C ‐alkylation to the C=N bond of the oxime group by a Lewis‐acid‐promoted reaction with a trialkylzincate or a dialkylzinc reagent. The O–N bond of the thus obtained adduct was reductively cleaved under hydrogenolysis in the presence of the Pd‐C catalyst to afford an α‐amino ester. Treatment of the oxime derivative prepared from methyl 5‐bromo‐2‐oxopentanoate with the trialkylzincate gave an α‐alkyl proline derivative via the addition reaction followed by the intramolecular attack upon a bromine‐bearing carbon. The reaction of ethyl 4‐oxo‐2‐pentynoate with hydroxylamine formed an isoxazole derivative by way of the intramolecular attack of an in situ‐generated oxime to the carbonyl group. From this isoxazole derivative, ethyl 2‐amino‐4‐oxo‐2‐pentenoate was given by the Pd‐C‐catalyzed hydrogenolysis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)