Asymmetric flow catalysis: Mix-and-go solid-phase Nd/Na catalyst for expeditious enantioselective access to a key intermediate of AZD7594

Akihito Nonoyama, Naoya Kumagai, Masakatsu Shibasaki

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

An anti-selective catalytic asymmetric nitroaldol reaction was implemented in a continuous-flow reaction platform for the synthesis of a key intermediate of a drug candidate. The requisite solid-phase catalyst was readily prepared by mixing an amide-based chiral ligand and inexpensive inorganic salts, NdCl3•6H2O and NaOtBu, without covalent bond linkages. The flow system was operated with 2-Me-THF as the eluent for ca. 400 h to provide a crude nitroaldol adduct in a highly stereoselective manner with no work-up procedure, reaching turnover number over 1600. Facile reduction of the nitro group of the product afforded a key intermediate of AZD7594, a therapeutic candidate for asthma and chronic obstructive pulmonary disease.

Original languageEnglish
Pages (from-to)1517-1521
Number of pages5
JournalTetrahedron
Volume73
Issue number11
DOIs
Publication statusPublished - 2017
Externally publishedYes

Keywords

  • Bimetallic catalyst
  • Flow reaction
  • Heterogeneous catalyst
  • Neodymium
  • Nitroaldol reaction

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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