For the preparation of compound libraries of Michael acceptors with tunable reactivity
toward nuclophilic selenocysteine residue of thioredoxin reductase, a range of 3-arylglutaconic
acids were required. The existing methods at the time had limited scope or involved
several steps. A hitherto undescribed protocol for direct palladium(II) acetate-catalyzed
arylation of glutaconic acid dimethyl ester at position 3 has been developed with
a diverse set of arenediazonium tosylates followed by hydrolysis. This generally good-yielding
two-step sequence displayed a propensity to deliver E-configured coupling products while compounds mostly featured in the literature were
predominantly Z-configured. The possibility for preparing a library of 4-arylpyridine-2,6(1H,3H)-diones has been exemplified.
Key words
arylpent-2-enedioic acids - glutaconic acid - diazonium tosylate - Pd-catalyzed coupling
- regiospecificity - ester hydrolysis - imide synthesis