Fujimoto–Belleau reaction
The Fujimoto–Belleau reaction is a chemical reaction that forms cyclic α-substituted α,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 Fujimoto-Belleau reaction](http://upload.wikimedia.org/wikipedia/commons/thumb/2/23/Fujimoto-Belleau_Reaction_Scheme.png/500px-Fujimoto-Belleau_Reaction_Scheme.png)
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 workup—i.e., aldol addition followed by an E1cB elimination of hydroxide occurs.[1]
![mechanism of the reaction](http://upload.wikimedia.org/wikipedia/commons/thumb/2/2f/Fujimoto-Belleau_reaction_mechanism.svg/550px-Fujimoto-Belleau_reaction_mechanism.svg.png)
Applications of the Fujimoto-Belleau reaction
[edit]Steroid synthesis
[edit]The Fujimoto–Belleau 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 Fujimoto–Belleau reaction invoked in steroid synthesis. Note that this pathway is not the true total syntheses for these steroids.
References
[edit]- ^ Wang, Zerong (September 15, 2010). "Fujimoto-Belleau Reaction". Comprehensive Organic Name Reactions and Reagents. doi:10.1002/9780470638859. ISBN 9780470638859.
- George I. Fujimoto (1951). "Labeling of Steroids in the 4-Position". J. Am. Chem. Soc. 73 (4): 1856. doi:10.1021/ja01148a518.
- Bernard Belleau (1951). "The Reaction of Methylmagnesium Iodide with β-(1-Hydroxy-3,4-dihydro-2-naphthyl)-butyric Acid Lactone". J. Am. Chem. Soc. 73 (11): 5441–5443. doi:10.1021/ja01155a504.
- Weill-Raynal, J. Synthesis 1969, 49.