Catalytic enantioselective synthesis of novel atropisomeric compounds having an N-C chiral axis and their application to asymmetric reaction

Masashi Takahashi, Osamu Kitagawa

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Atropisomeric compounds due to rotational restriction around an N-C bond have received much attention recently as novel chiral molecules. However, catalytic enantioselective synthesis of such N-C axially chiral compounds has not so far been reported. We succeeded in the highly enantioselective syntheses of atropisomeric ortho-tert-butyl anilides, lactams and indoles having an N-C chiral axis through chiral palladium-catalyzed N-C bond forming reactions. That is, in the presence of (R)-DTBM-SEGPHOS-Pd(OAc)2 catalyst, N-arylation (Buchwald-Hartwig amination) of achiral ortho-tert-butylanilides with p-iodonitrobenzene proceeded in a highly enantioselective manner (88-96% ee) to give atropisomeric N-(p-nitrophenyl)anilides in good yields. The application of the present catalytic enantioselective N-arylation to an intramolecular version gave atropisomeric lactam derivatives with high optical purity (92 -98%ee). The a-alkylation with the lithium enolate prepared from the atropisomeric anilide and lactam products with various alkyl halides proceeded with high diastereoselectivity (diastereomer ratio = 31 : 1-80 : 1). On the other hand, 5-endo-hydroaminocyclization of achiral ortho-alkynylanilines using (R)-SEGPHOS-PdCl2 catalyst afforded optically active atropisomeric indole derivatives (up to 83% ee) in good yields.

Original languageEnglish
Pages (from-to)985-993
Number of pages9
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Volume69
Issue number9
DOIs
Publication statusPublished - 2011 Sep

Fingerprint

Anilides
Lactams
Derivatives
Indoles
Amination
Catalysts
Alkylation
Palladium
Lithium
Molecules

Keywords

  • Anilide
  • Aromatic amination
  • Atropisomerism
  • Catalytic enantioselective reaction
  • Chiral phosphine
  • Hydroaminocyclization
  • Indole
  • Lactam
  • N-c chiral axis
  • Palladium

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

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title = "Catalytic enantioselective synthesis of novel atropisomeric compounds having an N-C chiral axis and their application to asymmetric reaction",
abstract = "Atropisomeric compounds due to rotational restriction around an N-C bond have received much attention recently as novel chiral molecules. However, catalytic enantioselective synthesis of such N-C axially chiral compounds has not so far been reported. We succeeded in the highly enantioselective syntheses of atropisomeric ortho-tert-butyl anilides, lactams and indoles having an N-C chiral axis through chiral palladium-catalyzed N-C bond forming reactions. That is, in the presence of (R)-DTBM-SEGPHOS-Pd(OAc)2 catalyst, N-arylation (Buchwald-Hartwig amination) of achiral ortho-tert-butylanilides with p-iodonitrobenzene proceeded in a highly enantioselective manner (88-96{\%} ee) to give atropisomeric N-(p-nitrophenyl)anilides in good yields. The application of the present catalytic enantioselective N-arylation to an intramolecular version gave atropisomeric lactam derivatives with high optical purity (92 -98{\%}ee). The a-alkylation with the lithium enolate prepared from the atropisomeric anilide and lactam products with various alkyl halides proceeded with high diastereoselectivity (diastereomer ratio = 31 : 1-80 : 1). On the other hand, 5-endo-hydroaminocyclization of achiral ortho-alkynylanilines using (R)-SEGPHOS-PdCl2 catalyst afforded optically active atropisomeric indole derivatives (up to 83{\%} ee) in good yields.",
keywords = "Anilide, Aromatic amination, Atropisomerism, Catalytic enantioselective reaction, Chiral phosphine, Hydroaminocyclization, Indole, Lactam, N-c chiral axis, Palladium",
author = "Masashi Takahashi and Osamu Kitagawa",
year = "2011",
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TY - JOUR

T1 - Catalytic enantioselective synthesis of novel atropisomeric compounds having an N-C chiral axis and their application to asymmetric reaction

AU - Takahashi, Masashi

AU - Kitagawa, Osamu

PY - 2011/9

Y1 - 2011/9

N2 - Atropisomeric compounds due to rotational restriction around an N-C bond have received much attention recently as novel chiral molecules. However, catalytic enantioselective synthesis of such N-C axially chiral compounds has not so far been reported. We succeeded in the highly enantioselective syntheses of atropisomeric ortho-tert-butyl anilides, lactams and indoles having an N-C chiral axis through chiral palladium-catalyzed N-C bond forming reactions. That is, in the presence of (R)-DTBM-SEGPHOS-Pd(OAc)2 catalyst, N-arylation (Buchwald-Hartwig amination) of achiral ortho-tert-butylanilides with p-iodonitrobenzene proceeded in a highly enantioselective manner (88-96% ee) to give atropisomeric N-(p-nitrophenyl)anilides in good yields. The application of the present catalytic enantioselective N-arylation to an intramolecular version gave atropisomeric lactam derivatives with high optical purity (92 -98%ee). The a-alkylation with the lithium enolate prepared from the atropisomeric anilide and lactam products with various alkyl halides proceeded with high diastereoselectivity (diastereomer ratio = 31 : 1-80 : 1). On the other hand, 5-endo-hydroaminocyclization of achiral ortho-alkynylanilines using (R)-SEGPHOS-PdCl2 catalyst afforded optically active atropisomeric indole derivatives (up to 83% ee) in good yields.

AB - Atropisomeric compounds due to rotational restriction around an N-C bond have received much attention recently as novel chiral molecules. However, catalytic enantioselective synthesis of such N-C axially chiral compounds has not so far been reported. We succeeded in the highly enantioselective syntheses of atropisomeric ortho-tert-butyl anilides, lactams and indoles having an N-C chiral axis through chiral palladium-catalyzed N-C bond forming reactions. That is, in the presence of (R)-DTBM-SEGPHOS-Pd(OAc)2 catalyst, N-arylation (Buchwald-Hartwig amination) of achiral ortho-tert-butylanilides with p-iodonitrobenzene proceeded in a highly enantioselective manner (88-96% ee) to give atropisomeric N-(p-nitrophenyl)anilides in good yields. The application of the present catalytic enantioselective N-arylation to an intramolecular version gave atropisomeric lactam derivatives with high optical purity (92 -98%ee). The a-alkylation with the lithium enolate prepared from the atropisomeric anilide and lactam products with various alkyl halides proceeded with high diastereoselectivity (diastereomer ratio = 31 : 1-80 : 1). On the other hand, 5-endo-hydroaminocyclization of achiral ortho-alkynylanilines using (R)-SEGPHOS-PdCl2 catalyst afforded optically active atropisomeric indole derivatives (up to 83% ee) in good yields.

KW - Anilide

KW - Aromatic amination

KW - Atropisomerism

KW - Catalytic enantioselective reaction

KW - Chiral phosphine

KW - Hydroaminocyclization

KW - Indole

KW - Lactam

KW - N-c chiral axis

KW - Palladium

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JO - Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry

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