Palladium-Catalyzed Chemoselective Protodecarboxylation of Polyenoic Acids

Abstract

Conditions for the first palladium-catalyzed chemoselective protodecarboxylation of polyenoic acids to give the desired polyenes in good yields are presented. The reactions proceed under mild conditions using either a Pd(0) or Pd(II) catalyst and tolerate a variety of aryl and aliphatic substitutions. Unique aspects of the reaction include the requirement of phosphines, water, and a polyene adjacent to the carboxylic acid.

Pd‐Catalyzed Synthesis of Vinyl Arenes from Aryl Halides and Acrylic Acid

“…[28] Hydrocarboxylation of 3y gave naproxen,anonsteroidal anti-inflammatory drug. This is in line with Croatt's mechanistic proposal fort he Pd/phosphine-catalyzedp rotodecarboxylation of polyenoic acids, [24] which involves ar eversible Michael addition of the phosphine to the unsaturated carboxylates. The kinetic profile of the vinylation of 1a showed that the substrates are rapidly consumed and that the postulated cinnamic acid intermediate 4a builds up in solution Scheme2.Mechanistic outline for the envisioned processes.…”

“…The key requirements of an effective catalytic system for the desired transformation were identified to be that it 1) is just active enough to catalyze the vinylation reaction with acrylic acid, 2) does not mediate any further coupling of the aryl bromide with styrenes or cinnamic acids, 3) effectively promotes the protodecarboxylation of cinnamic acids but not that of acrylic acid, and 4) operates under sufficiently mild conditions to avoid undesired oxidation or polymerization of substrates and/or products. Ideally, the decarboxylation would be promoted by the same palladium catalyst that mediates the cross‐coupling step …”

“…[20] Scheme 2d etails the mechanistic blueprint for this approach.T he electron-withdrawingC OOH group should facilitate aH eck-type vinylation of aryl halides with acrylic acid leading to the corresponding cinnamate. [24] In the search for ac atalytic system that fulfills the above requirements, 4-bromotoluene (1a)a nd acrylic acid (2)w ere chosen as models ubstrates, and variousb ases, ligands, and additivesw ere systematicallyi nvestigated (Table 1). [23] The key requirements of an effective catalytic system for the desired transformationw ere identified to be that it 1) is just active enough to catalyze the vinylation reactionw ith acrylic acid, 2) does not mediate any furtherc ouplingo ft he aryl bromide with styrenes or cinnamic acids, 3) effectively promotes the protodecarboxylation of cinnamic acids but not that of acrylic acid, and 4) operates under sufficiently mild conditions to avoid undesired oxidation or polymerization of substrates and/or products.…”

“…Ideally,t he decarboxylation would be promoted by the same palladium catalyst that mediates the cross-coupling step. [24] In the search for ac atalytic system that fulfills the above requirements, 4-bromotoluene (1a)a nd acrylic acid (2)w ere chosen as models ubstrates, and variousb ases, ligands, and additivesw ere systematicallyi nvestigated (Table 1).…”

Dienedioic acid as a useful diene building block via directed Heck-decarboxylate coupling

“…Quite interestingly, during the substrate scope investigation, a by-product 9-2 from the decarboxylation of 1-11 was isolated in 9% yield, evoking our suspension that this reaction might follow the "Decarboxylation-Heck type" mechanism. However, the background reaction without adding substrate 2-24 failed to yield any decarboxylation product 9-2, while~70% starting material 1-11 remained untouched 33 (Fig. 7c; Supplementary Fig.…”