Methyl-Selective α-Oxygenation of Tertiary Amines to Formamides by Employing Copper/Moderately Hindered Nitroxyl Radical (DMN-AZADO or 1-Me-AZADO)

Satoru Nakai, Takafumi Yatabe, Kosuke Suzuki, Yusuke Sasano, Yoshiharu Iwabuchi, Jun ya Hasegawa, Noritaka Mizuno, Kazuya Yamaguchi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Methyl-selective α-oxygenation of tertiary amines is a highly attractive approach for synthesizing formamides while preserving the amine substrate skeletons. Therefore, the development of efficient catalysts that can advance regioselective α-oxygenation at the N-methyl positions using molecular oxygen (O2) as the terminal oxidant is an important subject. In this study, we successfully developed a highly regioselective and efficient aerobic methyl-selective α-oxygenation of tertiary amines by employing a Cu/nitroxyl radical catalyst system. The use of moderately hindered nitroxyl radicals, such as 1,5-dimethyl-9-azanoradamantane N-oxyl (DMN-AZADO) and 1-methyl-2-azaadamanane N-oxyl (1-Me-AZADO), was very important to promote the oxygenation effectively mainly because these N-oxyls have longer life-times than less hindered N-oxyls. Various types of tertiary N-methylamines were selectively converted to the corresponding formamides. A plausible reaction mechanism is also discussed on the basis of experimental evidence, together with DFT calculations. The high regioselectivity of this catalyst system stems from steric restriction of the amine-N-oxyl interactions.

Original languageEnglish
Pages (from-to)16651-16659
Number of pages9
JournalAngewandte Chemie - International Edition
Volume58
Issue number46
DOIs
Publication statusPublished - 2019 Nov 11

Keywords

  • copper
  • formamides
  • methyl-selective α-oxygenation
  • nitroxyl radical
  • tertiary amines

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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