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

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 Bronsted acid. Specifically, a Bronsted acid and quinuclidine jointly catalyze the halo-cycloetherification of gamma-alkenyl alcohols with NIS or NBS, while only quinuclidine acts as a catalyst in the halolactonization of gamma-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.

Automated summary

In halogen chemistry, the reaction between amines and N-halosuccinimides is complex, with NIS mainly forming non-covalent halogen bonded amine complexes and similar behavior observed for NBS, requiring catalysis with an appropriate Brønsted acid.