The de Mayo Reaction

In 1962 Paul de Mayo (Univ. Western Ontario) found that the enol of pentane-1,3-dione gave a 2-acetyl-1-methylcyclobutanol adduct when irradiated in the presence of a cycloalkene. As shown by the top reaction in the following diagram, this cyclobutanol (R¹ = R² = CH₃) may then undergo a facile base-catalyzed retroaldol fragmentation to a 1,5-diketone. This sequence thus achieves the attachment of a short alkyl chain to each carbon atom of the double bond. Further base induced reactions, such as epimerization of the initial cis-configuration, and aldol cyclization of the diketone may follow. Following its initial report, this powerful [2+2]-cycloaddition reaction sequence has been put to many uses. One of these is the synthesis of γ-tropolone shown by the bottom equation.

Two additional applications of the de Mayo reaction in synthesis will be displayed above.

The upper reaction is noteworthy for the unexpectedly high regioselectivity of the [2+2] cycloaddition. Ring opening of the bicyclo[3.2.0]heptane moiety proceeds by an ethylagous elimination or Grob fragmentation. Conversion of the resulting bicyclic ketoacetal to β-himachalene was straightforward. The lower reaction demonstrates that poor stereoselectivity in the cycloaddition does not necessarily present a problem. Here, the four new stereocenters in the cycloadduct are lost and/or epimerized by the retroaldol opening of the four-membered ring and subsequent aldol cyclization.