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Protonation‐Assisted Conjugate Addition of Axially Chiral Enolates: Asymmetric Synthesis of Multisubstituted β‐Lactams from α‐Amino Acids
Author(s) -
Yoshimura Tomoyuki,
Takuwa Masatoshi,
Tomohara Keisuke,
Uyama Makoto,
Hayashi Kazuhiro,
Yang Pan,
Hyakutake Ryuichi,
Sasamori Takahiro,
Tokitoh Norihiro,
Kawabata Takeo
Publication year - 2012
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201201339
Subject(s) - protonation , conjugate , chemistry , intramolecular force , enantioselective synthesis , stereochemistry , combinatorial chemistry , medicinal chemistry , catalysis , organic chemistry , ion , mathematical analysis , mathematics
β‐Lactams with contiguous tetra‐ and trisubstituted carbon centers were prepared in a highly enantioselective manner through 4 ‐exo‐trig cyclization of axially chiral enolates generated from readily available α‐amino acids. Use of a weak base (metal carbonate) in a protic solvent (EtOH) is the key to the smooth production of β‐lactams. Use of the weak base is expected to generate the axially chiral enolates in a very low concentration, which undergo intramolecular conjugate addition without suffering intermolecular side reactions. Highly strained β‐lactam enolates thus formed through reversible intramolecular conjugate addition (4 ‐exo‐trig cyclization) of axially chiral enolates undergo prompt protonation by EtOH in the reaction media (not during the work‐up procedure) to give β‐lactams in up to 97 % ee .