New Paper - Convenient and efficient synthesis of 4-oxo-2-butenoic acids

RSC Adv., 2021, 11, 30229-30236

https://doi.org/10.1039/D1RA05539A

https://pubs.rsc.org/en/content/articlelanding/2021/                                                             RA/D1RA05539A

Mélanie Uguen, Conghao Gai, Lukas J. Sprenger, Hang Liu, Andrew G. Leach and Michael J. Waring*

4-Oxobutenoic acids are useful as biologically active species and as versatile intermediates for further derivatisation. Currently, routes to their synthesis can be problematic and lack generality. Reaction conditions for the synthesis of 4-oxo-2-butenoic acid by microwave-assisted aldol-condensation between methyl ketone derivatives and glyoxylic acid have been developed. They provide the desired products in moderate to excellent yields for a wide range of substrates, by applying a simple procedure to accessible starting materials. The investigation revealed different conditions are required depending on the nature of the methylketone substituent, with aryl derivatives proceeding best using tosic acid and aliphatic substrates reacting best with pyrrolidine and acetic acid. This substituent effect is rationalised by frontier orbital calculations. Overall, this work provides methods for synthesis of 4-oxo-butenoic acids across a broad range of substrates. 

Last modified: Mon, 19 Dec 2022 17:20:09 GMT