Stereodivergent synthesis of arylcyclopropylamines by sequential C-H borylation and Suzuki-Miyaura coupling

Shin Miyamura, Misaho Araki, Takayoshi Suzuki, Junichiro Yamaguchi, Kenichiro Itami

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

A step-economical and stereodivergent synthesis of privileged 2-arylcyclopropylamines (ACPAs) through a C-(sp3)-H borylation and Suzuki-Miyaura coupling sequence has been developed. The iridium-catalyzed C-H borylation of N-cyclopropylpivalamide proceeds with cis selectivity. The subsequent B-cyclopropyl Suzuki-Miyaura coupling catalyzed by [PdCl2(dppf)]/Ag2O proceeds with retention of configuration at the carbon center bearing the Bpin group, while epimerization at the nitrogen-bound carbon atoms of both the starting materials and products is observed under the reaction conditions. This epimerization is, however, suppressed in the presence of O2. The present new ACPA synthesis results in not only a significant reduction in the steps required for making ACPA derivatives, but also the ability to access either isomer (cis or trans) by simply changing the atmosphere (N2 or O2) in the coupling stage.

Original languageEnglish
Pages (from-to)846-851
Number of pages6
JournalAngewandte Chemie - International Edition
Volume54
Issue number3
DOIs
Publication statusPublished - 2015 Jan 12
Externally publishedYes

Fingerprint

Bearings (structural)
Carbon
Iridium
Atmosphere
Isomers
Nitrogen
Derivatives
Atoms
palladium chloride

Keywords

  • Boron
  • C-H activation
  • Cross-coupling
  • Iridium
  • Small ring systems

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Medicine(all)

Cite this

Stereodivergent synthesis of arylcyclopropylamines by sequential C-H borylation and Suzuki-Miyaura coupling. / Miyamura, Shin; Araki, Misaho; Suzuki, Takayoshi; Yamaguchi, Junichiro; Itami, Kenichiro.

In: Angewandte Chemie - International Edition, Vol. 54, No. 3, 12.01.2015, p. 846-851.

Research output: Contribution to journalArticle

Miyamura, Shin ; Araki, Misaho ; Suzuki, Takayoshi ; Yamaguchi, Junichiro ; Itami, Kenichiro. / Stereodivergent synthesis of arylcyclopropylamines by sequential C-H borylation and Suzuki-Miyaura coupling. In: Angewandte Chemie - International Edition. 2015 ; Vol. 54, No. 3. pp. 846-851.
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