Stereochemical evidence for stabilization of a nitrogen cation by neighboring chlorine or bromine

Neighboring group participation is one of the fundamental interactions in organic reactions and can influence the reaction rate, stereoselectivity, and reaction pathway through transient carbon-carbon or carbon-heteroatom bond formation. The latter category includes cyclic three- and five-membered bromonium ions, wherein lone-pair electrons of the monovalent bromine atom stabilize a trigonal carbocation. Although similar nucleophilic interactions of monovalent halogen atoms with non-carbon atom-centered cations have long been predicted, we know of no experimental evidence of such an interaction. Here, we demonstrate a nucleophilic interaction of neighboring monovalent halogen to stabilize an imino sp(2) nitrogen cation. This interaction has an overwhelming impact on the reaction pathway, completely altering the migratory preference under acid-catalyzed Beckmann rearrangement conditions. In sharp contrast to the general case of anti-migration, peri-chloro- and peri-bromo-substituted O-tosyl oximes of 1-tetralone substructures and their derivatives undergo syn-migration under Beck-mann rearrangement conditions (i.e., migration of the group on the syn side of the leaving group). The peri-chloro or peri-bromo neighboring group turned out to provide strong anchimeric assistance for syn-migration via transient formation of a cyclic five-membered imino-halonium cation with dissociation of tosylic acid. Thus, formation of the syn-migration products can be attributed to a reaction mechanism that is different from the conventional Beckmann rearrangement mechanism. That is, the positively charged imino nitrogen atom can be stabilized by, or interact with, a chloro or bromo group in close spatial proximity, and this interaction dramatically changes the reaction pathway, selectively affording regioisomeric lactams from closely related starting materials.