Hajos–Parrish–Eder–Sauer–Wiechert reaction

The Hajos- Parrish -Eder- Sauer-Wiechert reaction is a reaction in organic chemistry. This is a proline -catalyzed asymmetric aldol reaction. The reaction is named after its discoverers at the company Hoffmann -La Roche and Schering AG.

History

The original method was discovered by Zoltan Hajos and David R. Parrish in the 1970s and provides the optically active aldol product - a bicyclic ketol. The Eder- Sauer-Wiechert modification extended the reaction to a condensation step and the optically active enedione obtained on the way this organocatalytic reaction. The reaction, and the resulting chiral compounds have been widely utilized in steroid synthesis to build the C- and D- ring of the Steran skeleton. The reaction was also often used in the synthesis of other optically pure molecules.

Of course, in the original work proline is used as a chiral catalyst for aldol reaction occurring. The starting compound is an achiral triketone and there are only 3 mol% of (S )-proline used a ketol with 93 % enantiomeric excess produce. The employees worked at moderate temperatures and DMF as solvent. In contrast, the Schering group working under non-biological conditions, with 47 mol % (S) -proline in 1 N perchloric acid and acetonitrile as solvent at 80 ° C. It was therefore not the product is isolated by Hajos and Parrish found but instead the unsaturated product of the aldol condensation.

Hajos and Parrish have determined the absolute configuration of the cis -linked 7a -methyl-6 ,5- bicyclic ketol by CD spectroscopy and confirmed these results using the X-ray structure analysis. The structure of the ketol is therefore the following:

In 2000, a study by Benjamin List et al. demonstrated that an aldol between a ketone and an aldehyde in the presence of (S)- proline, also leads to an asymmetric induction with a significant enantiomeric excess.

The authors express the similarity between the proline-catalyzed asymmetric aldol reaction and the enzyme aldolase A way, because they both have an enamine intermediate as a transition state.

Reaction mechanism

There has been a number of suggestions on the mechanism of catalysis of asymmetric reactions. Hajos proposed in 1974 a hemiaminal as a key intermediate ago, due its tests with a stoichiometric amount of H218O water while Agami preferred an enamine as an intermediate in 1984. Through experimental results, he suggested an enamine with two proline molecules prior to as a transition state on the basis of the kinetic data. Correspondingly, proposed by Kendall Houk 2001 mechanism of the transition state. This ranges from a single proline molecule at the transition state by means of a hydrogen bond to be formed.

The reaction mechanism as it has in 2000, the group presented to playlist based on the formation of an enamine and the observed stereochemistry can be explained with the help of the Zimmerman -Traxler model.

Origin of the name of the reaction

In 1985 was designated as the first of C. Agami, the proline -catalyzed asymmetric Robinson annulation as Hajos- Parrish reaction. Henri Kagan also designated (along with Agami ) this reaction in a publication with this name. Later in 2001, Kagan published a work, and described the reaction here as Hajos- Parrish- Wiechert reaction. In 2002, two names has been added in a paper by Benjamin List and the reaction is now known practically uniform in the scientific literature as the Hajos- Parrish -Eder -Sauer- Wiechert reaction. The original method gives the optically active aldol product, known as Hajos - Parrish reaction.