6 - Intramolecular Hydrogen-Atom Abstraction

Abstract

Hydrogen-atom abstraction by oxygen-centered radicals via the Barton reaction involves irradiation of alkyl nitrite, RO–NO, with a mercury lamp generating the corresponding alkoxyl radical, RO• through homolytic cleavage of the weak O–N bond. The formed reactive alkoxyl radical abstracts a hydrogen atom to form a carbon-centered radical and a strong O–H bond, via a six-membered transition state (1,5-H shift) or seven-membered transition state (1,6-H shift). The formed carbon-centered radical reacts on the nitrogen atom of alkyl nitrite to give δ-nitrosoalcohol or ɛ-nitrosoalcohol, and alkoxyl radical again. This reaction takes place through a chain reaction. Generally, nitroso compounds tautomerize to oximes, when they have a hydrogen atom. Heating or photolytic treatment of N,N-dialkyl-N-haloamine in sulfuric acid or trifluoroacetic acid, followed by neutralization with a base, generates a pyrrolidine or piperidine skeleton. This is the Hofmann–Löffler–Freytag reaction, and the reaction comprises the formation of an electrophilic aminium radical, 1,5-H shift (6-membered transition state) or 1,6-H shift (7-membered transition state), formation of 4-haloalkyl ammonium or 5-haloalkyl ammonium, and its polar cyclization by neutralization with a base. Since the Barton reaction and the Hofmann–Löffler–Freytag reaction generate very reactive oxygen-centered and nitrogen-centered radicals, respectively, the next 1,5- and 1,6-hydrogen atom abstraction reaction readily happens. However, 1,5-H shift does not proceed effectively by carbon-centered radicals, because there is not so much energy difference between the C–H bond before and after 1,5-H shift.