Atropisomeric lactam chemistry: catalytic enantioselective synthesis, application to asymmetric enolate chemistry and synthesis of key intermediates for NET inhibitors

Masashi Takahashi, Hajime Tanabe, Tsuyoshi Nakamura, Daisuke Kuribara, Toshiyuki Yamazaki, Osamu Kitagawa

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

In the presence of (R)-SEGPHOS-Pd(OAc)2 catalyst, the intramolecular N-arylation of ortho-tert-butyl-NH-anilides possessing an iodophenyl group proceeded in a highly enantioselective manner (89-98% ee) to give optically active atropisomeric lactams having an N-C chiral axis. MPLC purification of the enantio-enriched lactam products using an achiral silica gel column led to a further increase in the enantiomeric purity (>99% ee). The reaction of the lithium enolate prepared from the optically active atropisomeric lactam with various alkyl halides gave α-substituted and α,α-disubstituted lactam products with high diastereoselectivity. α-Alkylated lactam derivatives were efficiently converted to key intermediates for the synthesis of an NET inhibitor.

Original languageEnglish
Pages (from-to)288-296
Number of pages9
JournalTetrahedron
Volume66
Issue number1
DOIs
Publication statusPublished - 2010 Jan 2

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Lactams
Anilides
Silica Gel
Lithium
Purification
Derivatives
Catalysts

Keywords

  • Alkylation
  • Atropisomerism
  • Diastereoselective
  • Enantioselective
  • Enolate
  • Lactams
  • Palladium

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

Atropisomeric lactam chemistry : catalytic enantioselective synthesis, application to asymmetric enolate chemistry and synthesis of key intermediates for NET inhibitors. / Takahashi, Masashi; Tanabe, Hajime; Nakamura, Tsuyoshi; Kuribara, Daisuke; Yamazaki, Toshiyuki; Kitagawa, Osamu.

In: Tetrahedron, Vol. 66, No. 1, 02.01.2010, p. 288-296.

Research output: Contribution to journalArticle

Takahashi, Masashi ; Tanabe, Hajime ; Nakamura, Tsuyoshi ; Kuribara, Daisuke ; Yamazaki, Toshiyuki ; Kitagawa, Osamu. / Atropisomeric lactam chemistry : catalytic enantioselective synthesis, application to asymmetric enolate chemistry and synthesis of key intermediates for NET inhibitors. In: Tetrahedron. 2010 ; Vol. 66, No. 1. pp. 288-296.
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