Solvent-Free Mizoroki-Heck Reaction Applied to the Synthesis of Abscisic Acid and Some Derivatives

Abstract

Abscisic acid (ABA) is a natural product, which is a well-known phytohormone. However, this molecule has recently exhibited interesting biological activities, emphasizing the need for a simple and direct access to new analogues based on the ABA framework. Our strategy relies on a pallado-catalyzed Mizoroki-Heck cross-coupling as key reaction performed in solvent and ligand free conditions. After a careful optimization, we succeeded in accessing various (E/Z)-dienes and (E/E/Z)-trienes in moderate to good yields without isomerization and applied the same approach to the synthesis of ABA in an environmentally sound manner.

New Trends in C–C Cross-Coupling Reactions: The Use of Unconventional Conditions

“…Solvent-free methodologies have been commonly used under MW irradiation or mechanochemical conditions often using supported reagents, achieving maximum conversion and minimizing wastes. Dumonteil et al described a Pd-catalyzed Mizoroki-Heck cross-coupling performed in solvent and ligand-free conditions for the synthesis of abscisic acid (ABA), a well-known phytohormone of great biological interest [52]. Upon optimization of the reaction parameters, various dienes and trienes were obtained in moderate-to-good yields without isomerization.…”

Concise and Practical Total Synthesis of (+)-Abscisic Acid

“…Table summarized the representative syntheses of ABA reported in the literature. Chiral ( R )-4-hydroxy-2,2,6-trimethylcyclohexan-1-ones or the corresponding diones with a chiral auxiliary were utilized for stereoselective introduction of the hydroxyl group by nucleophilic addition of the chain parts (entries 1–5). Fair to good selectivity (33–78% diastereomeric excess) was reported in these cases.…”

“…It is worth noting that superb 97% enantiomeric excess was obtained by Sharpless asymmetric epoxidation of the cyclic allylic alcohol (entries 6 and 7) to establish the required Z -configuration of the double bond. , Reformatsky reaction of 4-bromo-3-methyl-2-butenoic ester followed by lactonization was effectively utilized for appendage of the required dienyl acid to the cyclohexanecarbaldehyde. , …”

Catalyzed Mizoroki-Heck Reaction or C-H Activation

“…The authors succeeded to functionalize this kind of tetracyclic molecule by regioselective alkoxylation via C-H bond activation avoiding the standard pre-halogenation.Berteina-Raboin's group developed the first direct C-H arylation on C2 and C3 thiophene ring for a convenient one-pot synthesis of thienopyridine, thienopyrimidine, and thienopyrazine scaffolds [6].The attention paid to environmentally friendly methods in terms of the quantities of catalysts, ligands and solvents is currently indispensable. In this context, Shi, Nawaz, Zaman and Sun [7] summarized recent advances in enantioselective C-H activation/functionalization via Mizoroki-Heck reaction or Suzuki reaction. These are methodologies that are used to generate synthetic, hemisynthetic or natural compounds with high added value whether in medicinal chemistry or agrochemistry.…”

“…The attention paid to environmentally friendly methods in terms of the quantities of catalysts, ligands and solvents is currently indispensable. In this context, Shi, Nawaz, Zaman and Sun [7] summarized recent advances in enantioselective C-H activation/functionalization via Mizoroki-Heck reaction or Suzuki reaction. These are methodologies that are used to generate synthetic, hemisynthetic or natural compounds with high added value whether in medicinal chemistry or agrochemistry.…”