An Amine-Catalyzed Enantioselective [3+2] Cycloaddition of Azomethine Ylides and α,β-Unsaturated Aldehydes: Applications and Mechanistic Implications

• Published in: Chemistry : a European journal Vol. 18; no. 23; pp. 7179 - 7188
• Main Authors: Reboredo, Silvia, Reyes, Efraím, Vicario, Jose L., Badía, Dolores, Carrillo, Luisa, de Cózar, Abel, Cossío, Fernando P.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 04.06.2012; WILEY‐VCH Verlag
• Subjects: Aldehydes; Amines; asymmetric catalysis; Catalysts; Chains; Chemical reactions; Computation; Cycloaddition; organocatalysis; Precursors; pyrrolidines; reaction mechanisms
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201103015

The catalytic enantioselective [3+2] cycloaddition between azomethine ylides and α,β‐unsaturated aldehydes catalyzed by α,α‐diphenylprolinol has been studied in detail. In particular, the reaction has been extended to the use of 2‐alkenylidene aminomalonates generated in situ as azomethine ylide precursors. These reactions lead to the formation of pyrrolidines containing a 5‐alkenyl side chain with potential for chemical manipulation. Moreover, a detailed and concise computational study has been carried out to understand the exact nature of the mechanism of this reaction and especially the consequences derived from the incorporation of the chiral secondary amine catalyst on the reaction pathway. Wide ranging potential: The organocatalytic enantioselective [3+2] cycloaddition between azomethine ylides and enals has been extended to include 2‐alkenylideneaminomalonates as azomethine ylide precursors. The resulting pyrrolidines contain a 5‐alkenyl side chain with potential for further chemical manipulation (see scheme). Moreover, a detailed computational study reveals the nature of the reaction mechanism and the consequences derived from the incorporation of the catalyst on the reaction.