Flexible Entry into 3-Arylpent-2-enedioic Acids via Heck–Matsuda Arylation of Dimethyl Glutaconate with Arenediazonium Tosylates

Abstract

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.

Further Insight into the Castagnoli–Cushman-type Synthesis of 1,4,6-Trisubstituted 1,6-Dihydropyridin-2-(3H)-ones from 3-Arylglutaconic Acid Anhydrides

“…Alternatively, resonance stabilization of the anhydride’s enol form can provide a strong driving force for the enolization and the resulting CCR . Recently, we investigated a new type of highly reactive cyclic anhydrides for the CCR, namely, those of 3-arylglutaconic acids 5 . Anhydrides 4 are highly enolizable due to its being a “vinylogous malonate” in which the enol form 4′ is effectively stabilized by conjugation to the other carbonyl group (the nearby aryl group, likely providing additional stabilization).…”

“…The latter approach, of course, would require that anhydrides 4 and imines 1 be prepared in two separate (albeit distinctly straightforward) chemical operations. To investigate the yield and scope advantages of the two-component reactions of 4 with 1 , several 3-arylglutaconic anhydrides 4a – j were prepared from respective 3-arylglutaconic acids 5a – j as depicted in Scheme . Only with three acids ( 5a – c ), full conversion was achieved on simple reflux in toluene (Method A), leading to nearly quantitative yields.…”

Three‐Component Castagnoli‐Cushman Reaction of 3‐Arylglutaconic Acid Anhydrides, Carbonyl Compounds, and Ammonium Acetate: a Quick and Flexible Way to Assemble Polysubstituted NH‐δ‐lactams

“…Cyclic anhydrides 8 a – g were synthesized from 3‐arylgluraconic acids 12 a – g [21] using one of the two methods (Scheme 2): diacids 12 with electron‐neutral and electron‐rich aryl groups were efficiently cyclodehydrated on simple reflux in toluene with azeotropic removal of water (Method A); those with electron‐deficient aryl groups required being reacted for 2 days at room temperature with trifluoroacetic anhydride in acetonitrile in order to cyclize (Method B) [14] …”

Diazo Glutaconimides: an Unexplored Type of Heterocyclic α‐Diazocarbonyl Compounds Conveniently Evolved into Pyridine‐2,6(1H,3H)‐diones and Oxazolo[5,4‐b]pyridin‐5(4H)‐ones

“…Glutaconimides 5 , precursors of the target diazo compounds 4 , were obtained by analogy with the methods described in the literature [21] from synthetically available β‐substituted glutaconic acid anhydrides 6 [18–19] . Initial attempt at the Regitz diazo transfer using an equivalent amount of a base (DBU, TEA, DIPEA) resulted only in a negligible yield of 4 .…”

“…Compounds 3 have been shown to undergo metal carbene-mediated XÀ H insertion reactions [15] and [2 + 1] cycloaddition with aldehydes; [16] their synthetic potential continues being unraveled in our laboratories. [17] Recently we developed the synthesis of 3arylpent-2-enedioic (β-arylglutaconic) acids [18] and successfully employed them and their anhydrides in various multicomponent transformations. [19] This gave us an idea that the respective β-arylglutaconimides should be suitable substrates for the direct diazo transfer and, if so, would serve as synthetic precursors to α-diazo glutaconimides (4) which are isomeric to (E)-3-arylidene-4-diazopyrrolidine-2,5-diones 3 (Figure 1).…”