Proline-catalyzed aldol reactions

The Hajos–Parrish–Eder–Sauer–Wiechert and Barbas-List reactions in organic chemistry are a family of proline-catalysed asymmetric aldol reactions.

In the 1970s, two research groups discovered (and published) almost simultaneously their discoveries of two related intramolecular reactions: Zoltan Hajos and David Parrish at Hoffmann-La Roche and Rudolf Wiechert et al at Schering AG. The original Hajos-Parrish procedure begins with an achiral triketone in dimethylformamide and 3% (molar) catalytic (S)‑(−)‑proline. The product is a chiral ketol with 93% enantiomeric excess:

In the Eder-Sauer-Wiechert modification, the product shown above loses water to give the conjugated alkene.

Three decades later, Carlos Barbas and Benjamin List demonstrated that larger catalyst concentrates could enable a similar intermolecular reaction.

The reaction has seen extensive use in many enantiomerically-pure molecular syntheses. Indeed, it presaged the modern field of asymmetric organocatalysis.