Halogen Bonding of N-Halosuccinimides with Amines and Effects of Brønsted Acids in Quinuclidine-Catalyzed Halocyclizations

Jing Li, Eunsang Kwon, Martin James Lear, Yujiro Hayashi

Research output: Contribution to journalArticlepeer-review

Abstract

An arguable expectation in halogen chemistry is that an amine will react oxidatively with an N-halosuccinimide (NXS) to form an N-halogenated species bearing a covalent N−X bond. While likely for NCS under most conditions, we find this expectation simply not true for NIS and largely inaccurate for NBS. Herein, we disclose evidence through systematic NMR and X-ray studies that non-covalent halogen bonded amine complexes of NIS predominate over covalent N-halogenated species, even with primary and secondary amines. For example, during the catalytic electrophilic halocyclization of gem-disubstituted alkenes by cinchona-like amines, the quinuclidine complexes of NIS and NBS display lower reactivity than their parent N-halosuccinamides and require the presence of an appropriate Brønsted acid. Specifically, a Brønsted acid and quinuclidine jointly catalyze the halo-cycloetherification of γ-alkenyl alcohols with NIS or NBS, while only quinuclidine acts as a catalyst in the halolactonization of γ-alkenoic acids. Although our evidence confirms a transient N-halogenated quaternary ammonium salt as the halonium species, it is important to note that NIS predominantly forms ‘off-cycle’ halogen bonded amine complexes in solution.

Original languageEnglish
Article numbere2100080
JournalHelvetica Chimica Acta
Volume104
Issue number9
DOIs
Publication statusPublished - 2021 Sep

Keywords

  • amine catalyst
  • halocyclization
  • halogen bonding
  • halogens
  • iodine complex
  • reaction mechanisms

ASJC Scopus subject areas

  • Catalysis
  • Biochemistry
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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