Lewis Acid-Promoted 3-Aza-Cope Rearrangement of N-Alkyl-N-allylanilines

Article abstract of DOI:10.1021/jo00071a018

The 3-aza-Cope rearrangement of N-alkyl-N-alkylaniline substrates, which required 250 deg C to proceed thermally, was promoted by Lewis acid reagents at 111-140 deg C.Systematic studies of this reaction were performed to examine a number of reaction variables such as concentration, the stoichiometry of the Lewis acid with the substrate, the optimum temperature for rearrangement, and the type of Lewis acid reagent.Of the many Lewis acids investigated, ZnCl2 (140 deg C) and Et2O*BF3 (111 deg C) were the most generally successful reagents for promoting the aromatic 3-aza-Cope rearrangement.With respect to substrate variation, the presence of a methoxy substituent para to the N-allyl group slowed the reaction slightly, while a meta substituent accelerated the rate of <3,3> rearrangement and produced moderate site selectivity on the aromatic ring.Lewis acid-promoted rearrangement of an unsymmetrically substituted allyl moiety resulted in <3,3> sigmatropic rearrangement to give the 1-hexen-3-yl substituent on the aromatic ring.Overall, both ZnCl2 and Et2O*BF3 were shown to efficiently accelerate the regiospecific 3-aza-Cope rearrangement of N-alkyl-N-allylanilines for the purpose of forming a carbon-carbon bond between a secondary alkyl substituent and an aromatic ring.