de Mayo reaction

What is de Mayo reaction?

The de Mayo reaction was first described by de Mayo in 1962. It is a two-step process that involves the [2+2] photocycloaddition of an enol of a 1,3-dicarbonyl compound (such as a β-diketone, β-dialdehyde, or β-ketoaldehyde) with an olefin to produce a cyclobutanol intermediate, which then undergoes retro aldol condensation to form 1,5-dicarbonyl compounds. This reaction is sometimes referred to as the de Mayo photocycloaddition.

de Mayo reaction - general reaction scheme
de Mayo reaction

The regiochemistry of the cycloaddition in this reaction is predictable, except when there is extreme steric hindrance. The regioselectivity is also influenced by the solvent used. When an electron-deficient, polarized olefin (such as CH2=CHR, where R = CN, Cl, COCH3, CO2CH3, etc.) is subjected to the [2+2] photocycloaddition with the enol of a 1,3-dicarbonyl compound, the preferred product is the head-to-tail regioisomer with exo-orientation of R on the olefin.

However, when dealing with unsymmetrical 1,3-dicarbonyl compounds, the regioselectivity of the enolization can become a significant problem, and the reaction pattern may need to be modified using β-keto esters. Dioxolenones are used as a covalently locked enol form of a β-keto ester to prevent the formation of oxetanes, which result from the competing Paterno-Büchi reaction.

It should be noted that the cyclobutanol intermediate from cyclic 1,3-dicarbonyl compounds can be transformed into either cyclooctanedione or cyclohexenone (via an aldol reaction).

The application of de Mayo reaction is extensive when it comes to creating 1,5-dicarbonyl compounds, and it is particularly notable for its ability to synthesize the smallest known bicyclic compound ([4.3.1] undecane) with a trans bridgehead hydrogen.

References

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