can be used as acceptors. Overall, Michael acceptors are generally activated olefins such as those shown below where EWG refers to an electron withdrawing group such as cyano, keto, or ester as shown. Wichterle reaction The Wichterle reaction is a variant of the Robinson annulation that replaces methyl vinyl ketone with 1,3-dichloro-cis-2-butene. This gives an example of using a different Michael acceptor from the typical α,β-unsaturated ketone. The 1,3-dichloro-cis-2-butene is employed to avoid undesirable polymerization or condensation during the Michael addition. Hauser annulation The reaction sequence in the related Hauser annulation is a Michael addition followed by a Dieckmann condensation and finally an elimination. The Dieckmann condensation is a similar ring closing intramolecular chemical reaction of diesters with base to give β-ketoesters. The Hauser donor is an aromatic sulfone or methylene sulfoxide with a carboxylic ester group in the ortho position. The Hauser acceptor is a Michael acceptor. In the original Hauser publication ethyl 2-carboxybenzyl phenyl sulfoxide reacts with pent-3-ene-2-one with LDA as a base in THF at −78 °C. Asymmetric Robinson annulation Asymmetric synthesis of Robinson annulation products most often involve the use of a proline catalyst. Studies report the use of L-proline as well as several other chiral amines for use as catalysts during both steps of the Robinson annulation reaction. The advantages of using the optically active proline catalysis is that they are stereoselective with enantiomeric excesses of 60–70%. Wang, et al. reported the one-pot synthesis of chiral thiochromenes by such an organocatalytic Robinson annulation. Applications to synthesis The Wieland–Miescher ketone is the Robinson annulation product of 2-methyl-cyclohexane-1,3-dione and methyl vinyl ketone. This compound is used in the syntheses of many steroids possessing important biological properties and can be made enantiopure using proline catalysis. F. Dean Toste and co-workers have used Robinson annulation in the total synthesis of (+)-fawcettimine, a tetracyclic Lycopodium alkaloid that has potential application to inhibiting the acetylcholine esterase. Enantioselective route to platensimycin Scientists at Merck discovered platensimycin, a novel antibiotic lead compound with potential medicinal applications as seen in the adjacent picture. Initial synthesis gave a racemic form of the compound using an intramolecular etherification reaction of the alcohol motifs and the double bond. Yamamoto and coworkers report the use of an alternative intramolecular Robinson annulation to provide a straightforward enantioselective synthesis of tetracyclic core of platensimycin. The key Robinson annulation step was reported to be accomplished in one pot using L-proline for