STUDIES OF THE REGIOSPECIFIC 3-AZA-COPE REARRANGEMENT PROMOTED BY ELECTROPHILIC REAGENTS

The 3-aza-Cope rearrangement of N-alkyl-N-allyl enamine substrates, which required temperatures of 250 250-degrees-C to proceed thermally, was promoted at 111-degrees-C in the presence of electrophilic reagents such as HCl (0.5 equiv) TiCl4 (0.2 equiv), AlMe3 (1.2 equiv), or (ArO)2AlMe (1.2 equiv). In order to probe the regioselectivity of this accelerated carbon-carbon bond forming process under these reaction conditions, several enamine substrates were prepared from both isobutyraldehyde and cyclohexanone. Each substrate used in these studies was prepared having an unsymmetrical N-allylic group, substituted with either an alkyl or phenyl substituent at the 4 or 6 position of the 3-aza-Cope framework. In all cam examined, reaction acceleration by the electrophilic reagent produced regiospecific [3,3] rearrangement to the corresponding products resulting from [1,3] rearrangement were not observed. Hydride reduction of the resulting imines generated the delta,epsilon-unsaturated amines in 55-94% overall yield in the three-step condensation-rearrangement-reduction process from the secondary allylamine.