Robinson annulation

The Robinson annulation is a name reaction in organic chemistry and named after the British chemist and winner of the Nobel Prize in Chemistry, Robert Robinson. The reaction makes it possible to convert ketones and α, β -unsaturated ketones in a basic medium. Here, a six-membered ring is formed, and allowing organic compounds to extend a six-membered ring. Other ring sizes are not possible. The Robinson annulation consists of two crucial reaction steps: a Michael addition and subsequent aldol condensation.

Reaction mechanism

The Robinson annulation is explained in this section on the basis of a cyclohexanone derivative and an unsaturated pentanone.

The first steps of the Robinson annulation are the Michael addition of the same. The cyclohexanone derivative 1 is first deprotonated with base catalysis, so that nucleophilic attack of the α, β -unsaturated ketone can be carried out. After protonation of a 1,5 -diketone produced 4 The next steps include an aldol reaction. The 1,5 -diketone 4 turn is deprotonated by base catalysis, followed by ring closure occurs (6). After protonation of the β -hydroxy ketone 7, the α, β -unsaturated ketone 8 results in the elimination of water forms.

After completion of the reaction arises again an unsaturated carbonyl compound that can serve as a starting point for further Robinson annulation as so-called Michael acceptor. This method is particularly suitable for the synthesis of steroid scaffolds.

Variants

The Wieland - Miescher ketone is racemic itself. When the Robinson annulation catalyzed However with the help of L- or D- proline - so using a chiral enantiomerically pure organic catalyst - arises in an enantioselective reaction ( Hajos- Parrish -Eder -Sauer- Wiechert reaction called ) the (R) - or (S) - enantiomer of the Wieland-Miescher ketone preferred.