Muconates, nucleophilic additions

This work was repeated by several groups in the reaction of sodium dimethyl-malonate with methyl sorbate, Farmer and Metha observed small amounts of the 1,4-adduct besides the 1,6-addition product. Difficulties in conducting the transformations and analyzing the products are evident from reports on malonate additions to ethyl muconate depending on the reaction conditions, the expected 1,4-adduct (equation 4) or isomerization products formed by double bond displacement were isolated. Nucleophilic 1,4- and 1,6-addition reactions to 2,4-pentadienenitrile were also repor-... 

If we compare the estimated enthalpies of formation (Table 1) for (Z,Z)-mucon-aldehyde (14a) and rroRj-cyclobutene-l,2-dicarboxaldehyde (see Eq. 4), we find that the isomerization to 22b is endothermic by 16.9 kcal/mol, about 11 kcal/mol more endothermic than isomerization to the 2f/-pyran 19. This plausibly explains the rapid Z,Z to Z,E isomerization coupled with very slow Z, to , isomerization in the absence of nucleophiles. Thus, the first step could be unimolecular thermal rearrangement, while the second step under metabolic conditions could be the reversible Michael addition-isomerization. Of course, both steps could result from attack by nucleophiles either in the medium or on biological macromolecules. 

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