LEWIS ACID-PROMOTED 3-AZA-COPE REARRANGEMENT OF N-ALKYL-N-ALLYLENAMINES

The 3-aza-Cope rearrangement of the N-alkyl-N-allylenamines derived from isobutyraldehyde, which proceeds thermally at 250-degrees-C, has been accelerated by a variety of electrophilic reagents to give gamma,delta-unsaturated imines. Protic acids, such as HCl (0.5 equiv), and the Lewis acidic reagents TiCl4 (0.1-0.2 equiv), Et2O.BF3 (0.5 equiv), and AlMe3 (1.0 equiv) produced complete [3,3] rearrangement of substrates at 111-degrees-C. By increasing the Lewis acidity of the aluminum reagents, this transformation was achieved at 50-degrees-C with ClAlMe2, Cl2AlMe, and methylaluminum bis(2,6-diphenylphenoxide). Reaction conditions were studied initially by GLC analysis of the N-isobutyl derivative. These optimum conditions were then used to obtain isolated yields of 59-99% for rearrangement and in situ LiAlH4 reduction of the analogous N-methylcyclohexyl substrate to the corresponding delta,epsilon-unsaturated amine. Substrates derived from 2-phenylpropanal, n-butanal, cyclohexanone, and cyclopentanone were used to examine the general effectiveness of HCl, TiCl4, and AlMe3 as reagents for acceleration of the [3,3] rearrangement. The most versatile and efficient reagent for promoting this reaction, AlMe3, produced overall yields of 83-96% for the two-step rearrangement and reduction of these substrates.