Protonation-assisted conjugate addition of axially chiral enolates: Asymmetric synthesis of multisubstituted β-lactams from α-amino acids

Tomoyuki Yoshimura, Masatoshi Takuwa, Keisuke Tomohara, Makoto Uyama, Kazuhiro Hayashi, Pan Yang, Ryuichi Hyakutake, Takahiro Sasamori, Norihiro Tokitoh, Takeo Kawabata

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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. Inherently chiral enolates: β-Lactams with contiguous tetra- and trisubstituted carbon centers were prepared in a highly enantioselective manner starting from α-amino acids through axially chiral enolates (see scheme; PMB=p-methoxybenzyl). The use of a weak base (metal carbonate) in a protic solvent (EtOH) is the key to smooth production of β-lactams.

Original languageEnglish
Pages (from-to)15330-15336
Number of pages7
JournalChemistry - A European Journal
Volume18
Issue number48
DOIs
Publication statusPublished - Nov 26 2012
Externally publishedYes

Fingerprint

Lactams
Protonation
Amino acids
Amino Acids
Carbonates
Cyclization
Carbon
Metals

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Organic Chemistry

Cite this

Protonation-assisted conjugate addition of axially chiral enolates : Asymmetric synthesis of multisubstituted β-lactams from α-amino acids. / Yoshimura, Tomoyuki; Takuwa, Masatoshi; Tomohara, Keisuke; Uyama, Makoto; Hayashi, Kazuhiro; Yang, Pan; Hyakutake, Ryuichi; Sasamori, Takahiro; Tokitoh, Norihiro; Kawabata, Takeo.

In: Chemistry - A European Journal, Vol. 18, No. 48, 26.11.2012, p. 15330-15336.

Research output: Contribution to journalArticle

Yoshimura, T, Takuwa, M, Tomohara, K, Uyama, M, Hayashi, K, Yang, P, Hyakutake, R, Sasamori, T, Tokitoh, N & Kawabata, T 2012, 'Protonation-assisted conjugate addition of axially chiral enolates: Asymmetric synthesis of multisubstituted β-lactams from α-amino acids', Chemistry - A European Journal, vol. 18, no. 48, pp. 15330-15336. https://doi.org/10.1002/chem.201201339
Yoshimura, Tomoyuki ; Takuwa, Masatoshi ; Tomohara, Keisuke ; Uyama, Makoto ; Hayashi, Kazuhiro ; Yang, Pan ; Hyakutake, Ryuichi ; Sasamori, Takahiro ; Tokitoh, Norihiro ; Kawabata, Takeo. / Protonation-assisted conjugate addition of axially chiral enolates : Asymmetric synthesis of multisubstituted β-lactams from α-amino acids. In: Chemistry - A European Journal. 2012 ; Vol. 18, No. 48. pp. 15330-15336.
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