AZA-CLAISEN REARRANGEMENTS INITIATED BY ACID-CATALYZED MICHAEL ADDITION

The reaction of allylic amines with dimethyl acetylenedicarboxylate is subject to protic acid catalysis and affords 15, the product of Michael addition and aza-Claisen rearrangement. The sequence involves Michael addition of 4c or 19-21 to generate an intermediate N-alkenylammonium salt 14 that undergoes a charge-accelerated rearrangement to 15. Toluenesulfonic acid is a useful catalyst for the Michael addition step. Benzoic acid is not effective because the intermediate 14 is competitively dealkylated by the benzoate counterion. In one case, the intermediate N-alkenylammonium ion 18 has been detected by H-1 NMR spectroscopy and has been observed to undergo the aza-Claisen rearrangement at -20-degrees-C. The sequence of Michael addition and rearrangement can also be catalyzed by Lewis acids. This variation affords 15 at temperatures below -40-degrees-C. Finally, the Michael addition, aza-Claisen sequence has been applied to cyclic allylic amines 11 and 35, resulting in ring expansion products 12, 36, and 37.