The Hajos–Parrish–Eder–Sauer–Wiechert synthesis

In the early 1970s, two pharmaceutical industry groups (Hajos and Parrish at Hoffmann-La Roche; Eder, Sauer and Wiechert at Schering) discovered that (S)-proline catalyses the intramolecular aldol condensation of an achiral triketone with very high enantioselectivity.

The triketone, obtained by Michael addition of 2-methylcyclopentane-1,3-dione to methyl vinyl ketone, cyclizes with 3 mol% proline in DMF; the ketol is dehydrated in acid to give the Hajos–Parrish ketone in 93% ee. Proline chooses one of the two enantiotopic carbonyls of the ring. This intermediate has been used in the industrial synthesis of steroids, and the reaction is the forerunner of modern organocatalysis.