Ni(I)-Catalyzed Reductive Cyclization of 1,6-Dienes: Mechanism-Controlled trans Selectivity

Yulong Kuang, David Anthony, Joseph Katigbak, Flaminia Marrucci, Sunita Humagain, Tianning Diao

Research output: Contribution to journalArticlepeer-review

Abstract

A Ni-catalyzed reductive cyclization of 1,6-dienes affords 3,4-disubstituted cyclopentane and pyrrolidine derivatives with high trans diastereoselectivity. This cyclization reaction enables the efficient synthesis of trans-3,4-dimethyl gababutin, a pharmaceutical lead for treating neuropathic pain, and trans-3,4-dimethylpyrrolidine, a precursor to drug candidates and pesticides. The trans selectivity distinguishes this reaction from relevant precedents that proceed via hydrogen-atom transfer and lead to cis products. Mechanistic investigation, including kinetic, spectroscopic, and radical clock studies, attributes the trans diastereoselectivity to a classic, organometallic catalytic cycle mediated by Ni(I) and Ni(III) intermediates. The electron-rich Ni(I) intermediate, stabilized by a redox-active α-diimine ligand, is responsible for the chemoselectivity toward reductive cyclization as opposed to the redox-neutral cycloisomerization observed with previous Ni(II) catalysts.

Original languageEnglish (US)
Pages (from-to)268-280
Number of pages13
JournalChem
Volume3
Issue number2
DOIs
StatePublished - Aug 10 2017

Keywords

  • Ni(I) and Ni(III) intermediates
  • mechanism
  • nickel catalysis
  • trans-diastereoselective

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry
  • Environmental Chemistry
  • Chemical Engineering(all)
  • Biochemistry, medical
  • Materials Chemistry

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