One Pot, Six Chiral Centers

By using an amine-based catalyst, researchers at Aarhus University, in Denmark, have sculpted six chiral centers into a molecule in one fell swoop (Chem. Commun., DOI: 10.1039/b806418k). Beginning with an unsaturated aldehyde and a tricarbonyl compound, neither of which contain stereocenters, Karl Anker Jørgensen and colleagues developed reaction conditions that form just one bicyclic product out of 64 possible stereoisomers. The team chose a proline derivative featuring a silicon-protected hydroxyl group as the catalyst and added benzoic acid and the cyclic amine base piperidine to help carry out the transformation. The mechanism of the one-pot reaction is not yet clear, but the process generates four carbon-carbon bonds and six chiral centers with excellent selectivity, making a fused ring system found in compounds that show antitumor activity. The method works with a range of aldehydes (one example shown), but aromatic aldehydes gave the best yields. The reaction is "very impressive," says catalysis expert Miguel A. Yus at the University of Alicante, in Spain, noting that the Aarhus team can make products on a gram scale and purify them by crystallization.