Aza-Claisen Rearrangements Initiated by Acid-Catalyzed Michael Addition

• Published in: Journal of the American Chemical Society Vol. 116; no. 2; pp. 579 - 588
• Main Authors: Vedejs, Edwin, Gingras, Marc
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.01.1994; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Exact sciences and technology; Organic chemistry; Physical Sciences; Science & Technology; ASYMMETRIC INDUCTION; 3-AZA-COPE REARRANGEMENT; N-ALLYLKETENE N,O-ACETALS; RING-SYSTEMS; ALLYLENAMINES; DIENOPHILES; SALTS; CYCLIZATION; Michael addition; Solvent effect; Catalytic reaction; Aliphatic compound; Nitrogen heterocycle; Enamine; Tertiary amine; Acid catalysis; Claisen rearrangement; Experimental study; Allylic compound
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja00081a019

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.