Get access

The Elusive Enamine Intermediate in Proline-Catalyzed Aldol Reactions: NMR Detection, Formation Pathway, and Stabilization Trends


  • This work was supported by the DFG (SPP 1179). Scholarships by the Cusanuswerk and the Studienstiftung des deutschen Volkes are gratefully acknowledged. We thank the anonymous referees of this manuscript for exceptionally helpful and constructive suggestions.


original image

The missing link: The elusive enamine intermediate of nucleophilic proline catalysis was detected and stereochemically characterized by NMR analysis of the aldehyde self-aldolization reaction in dipolar aprotic solvents. NMR exchange spectroscopy (EXSY) was used to observe direct enamine formation from oxazolidinones. Additionally, the stabilization of the intermediate by the appropriate choice of solvent and substitution pattern on the aldehyde is presented.