Transnitrilation from Dimethylmalononitrile to Aryl Grignard and Lithium Reagents: A Practical Method for Aryl Nitrile Synthesis

Jonathan T. Reeves*, Christian A. Malapit, Frederic G. Buono, Kanwar P. Sidhu, Maurice A. Marsini, C. Avery Sader, Keith R. Fandrick, Carl A. Busacca, Chris H. Senanayake

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

An electrophilic cyanation of aryl Grignard or lithium reagents, generated in situ from the corresponding aryl bromides or iodides, by a transnitrilation with dimethylmalononitrile (DMMN) was developed. DMMN is a commercially available, bench-stable solid. The transnitrilation with DMMN avoids the use of toxic reagents and transition metals and occurs under mild reaction conditions, even for extremely sterically hindered substrates. The transnitrilation of aryllithium species generated by directed ortho-lithiation enabled a net C-H cyanation. The intermediacy of a Thorpe-type imine adduct in the reaction was supported by isolation of the corresponding ketone from the quenched reaction. Computational studies supported the energetic favorability of retro-Thorpe fragmentation of the imine adduct. (Chemical Equation Presented).

Original languageEnglish (US)
Pages (from-to)9481-9488
Number of pages8
JournalJournal of the American Chemical Society
Volume137
Issue number29
DOIs
StatePublished - Jul 29 2015
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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