Synthetic approaches towards 4-ylidenebutenolides and 4-ylidenetetronic acids. Regioselective nucleophilic additions to unsymmetrically substituted maleic anhydrides

Abstract

The application of unsymmetrically substituted maleic anhydrides in the synthesis of but-2-enolides, 4-hydroxybut-2-enolides, 4-ylidenebut-2-enolides, and 4-ylidenetetronic acid derivatives is examined. Reduction of 2-methylmaleic anhydride with metal hydride agents leads to a mixture of but-2-enolides (8a) and (8b), and 4-hydroxybut-2-enolides (7a) and (7b) corresponding to ca. 88% regioselective hydride ion attack at the more hindered (C-1) carbonyl function in the anhydride. Similar reductions of methoxy-substituted anhydrides (13) and (16) were completely regioselective and led to tetronic acid and 4-hydroxytetronic acid products resulting from hydride ion attack at only C-1 in the anhydrides.

Condensation of the phosphorane (22a) with 2-methylmaleic anhydride produced largely the E-ylidenebutenolide (23), accompanied by smaller amounts of the Z-butenolides (24) and (25) : similar condensations with the anhydrides (16a) and (16b) were totally regioselective and produced Z,E-mixtures of ylidenetetronic acids corresponding to attack at C-1 in the anhydrides. The addition of ethylmagnesium bromide to 2-methylmaleic anhydride, followed by dehydration of the intermediate carbinol, led to a 3 : 2 mixture of the ylidenebut-2-enolides (39) and (40), whereas the corresponding reaction with the 2-methoxy-anhydride (16b) was more selective producing only (41).

These studies have provided a basis for the development of syntheses of the ‘pulvinone,’‘pulvinic acid,’ and ‘multicolic acid’ groups of natural pigments.