Asymmetric Synthesis of Spiropyrazolones by Sequential Organo- and Silver Catalysis

• Published in: Angewandte Chemie International Edition Vol. 55; no. 5; pp. 1797 - 1800
• Main Authors: Hack, Daniel, Dürr, Alexander B., Deckers, Kristina, Chauhan, Pankaj, Seling, Nico, Rübenach, Lukas, Mertens, Lucas, Raabe, Gerhard, Schoenebeck, Franziska, Enders, Dieter
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 26-01-2016; Wiley Subscription Services, Inc; John Wiley & Sons, Ltd
• Edition: International ed. in English
• Subjects: Alkynes; Asymmetric synthesis; Catalysis; Chemical synthesis; Communications; Computational chemistry; Computer applications; Conia-ene reaction; organocatalysis; Oxidation; pyrazolones; Silver; silver catalysis; Conia-ene reaction; organocatalysis; silver catalysis; asymmetric synthesis; pyrazolones
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201510602

A stereoselective one‐pot synthesis of spiropyrazolones through an organocatalytic asymmetric Michael addition and a formal Conia‐ene reaction has been developed. Depending on the nitroalkene, the 5‐exo‐dig‐cyclization could be achieved by silver‐catalyzed alkyne activation or by oxidation of the intermediate enolate. The mechanistic pathways have been investigated using computational chemistry and mechanistic experiments.
Silver lining: A stereoselective one‐pot synthesis of spiropyrazolones through an organocatalytic asymmetric Michael addition and a formal Conia‐ene reaction has been developed. Silver catalysis plays a pivotal role for the cyclization, however metal‐free alternatives have been found in some cases. The mechanism was investigated by quantum chemical computations. H‐Do=hydrogen‐bonding donor.