Proline organocatalysis

This theme is often considered the starting point for the area of organocatalysis, even though early discoveries went unappreciated.

[2]: 5574 [3] Proline catalysis was initially reported by groups at Schering AG and Hoffmann-La Roche.

[1][4][5][6] Proline's chiral structure enables enantioselective synthesis, favoring a particular enantiomer or diastereomer.

[34] Illustrating an enolexo intramolecular aldolization, dicarbonyl (dials,diketones) can be converted to anti-aldol products with a 10% L-proline catalyst loading.

[37] As refined by List and Notz, the aforementioned reaction produces diol products as follows:[38] Proline-catalyzed aldol additions proceed via a six-membered enamine transition state according to the Zimmerman-Traxler model.

An enantioselective intramolecular aldol reaction.
An enantioselective intramolecular aldol reaction.
Intramolecular aldolization of a dialdehyde via an enamine intermediate.
Intramolecular aldolization of a dialdehyde via an enamine intermediate.
Proline-catalyzed asymmetric aldol reaction
Proline-catalyzed asymmetric aldol reaction
A six-membered transition state in asymmetric proline catalysis.
A six-membered transition state in asymmetric proline catalysis.
The chair transition state controls, in part, whether the enolexo or the enolendo product forms.
The chair transition state controls, in part, whether the enolexo or the enolendo product forms.