Enantioselective Aldol

Background Colour:

Sn2

Click the structures and reaction arrows in sequence to view the 3D models and animations respectively

Enantioselective intramolecular aldol cyclisation catalysed by proline. The first step of the reaction is enamine formation with S-proline and the ketone. Aldol cyclization occurs via a very stable (S,S) transition state. This cyclisation determines the stereochemistry of the product, i.e. the reaction is enantioselective. This forms iminium (S,S), which is then hydrolysed to form the product.

 

Fernando R. Clemente and K. N. Houk, Computational Evidence for the Enamine Mechanism of Intramolecular Aldol Reactions Catalyzed by Proline, Angew. Chem. Int. Ed. 2004, 43, 5765, DOI:10.1002/anie.200460916.