Hajos–Parrish–Eder–Sauer–Wiechert reaction

The Hajos–Parrish–Eder–Sauer–Wiechert reaction in organic chemistry is a proline catalysed asymmetric aldol reaction. The reaction is named after its principal investigators, Zoltan Hajos others, from Hoffmann-La Roche and Schering AG. Discovered in the 1970s the original Hajos-Parrish catalytic procedure - shown in the reaction equation - leading to the optically active bicyclic ketol as well as the Eder-Sauer-Wiechert modification leading to the optically active enedione through the loss of water from the ketol paved the way of asymmetric organocatalysis. It has been used extensively as a tool in the synthesis of steroids and other enantiomerically pure molecules.

Figure 1.

In the original reaction shown in Figure 1. naturally occurring chiral proline is the chiral catalyst in an Aldol reaction. The starting material is an achiral triketone and it requires just 3% of proline to obtain the reaction product, a ketol in 93% enantiomeric excess. As shown above, Hajos and Parrish worked at ambient temperature in dimethylformamide (DMF) solvent using a catalytic amount (3% molar equiv.) of (S)-(−)-proline enabling them to isolate the optically active intermediate bicyclic ketol. Thus, they described the first use of proline in a catalytic asymmetric aldol reaction.

The Schering group worked under non biological conditions using (S)-Proline (47 mol%), 1N perchloric acid, in acetonitrile at 80 °C. Hence, they could not isolate the Hajos, Parrish intermediate bicyclic ketol but instead the condensation product (S)-7a-methyl-2,3,7,7a-tetrahydro-1H-indene-1,5(6H)-dione through the loss of water. Thirty-seven years later a new group at Schering AG published the continuation of the earlier Schering work . Instead of the aforementioned non biological conditions the new group used the Hajos-Parrish catalytic procedure. Thus, they could isolate the optically active 6,5-bicyclic ketol described so far only in the Hajos-Parrish publications .

...
Wikipedia