The FujimotoâBelleau reaction is a chemical reaction that forms cyclic Îą-substituted Îą,β-unsaturated ketones from enol lactones. The reaction was discovered in 1951 by George I. Fujimoto and Bernard Belleau. Belleau used this reaction to synthesize 1-methyl-3-keto-1,2,3,9,10,10a-hexahydrophenanthrene from a ketoacid starting material and Fujimoto demonstrated that steroids could be synthesized from naturally occurring lactone species using this method as well.
The reaction starts with an nucleophilic acyl substitution via the Grignard reaction, opening the ring and forming an enolate. A proton transfer occurs, forming another enolate via deprotonation of the carbon atom attached to the R group. Using the enolate, an aldol condensation then occurs with aqueous or acidic workupâi.e., aldol addition followed by an E1cB elimination of hydroxide occurs. [1]
The FujimotoâBelleau reaction is used in commonly used in steroid synthesis. The reaction can be employed in the syntheses of steroids such as cholestenone, testosterone, and cortisone. Below is a scheme for the FujimotoâBelleau reaction invoked in steroid synthesis. Note that this pathway is not the true total syntheses for these steroids.