Improved synthesis of bioactive stilbene derivatives applying design of experiments to the Heck–Matsuda reaction

Abstract

Design of experiments (DOE) was instrumental to optimize reaction conditions which allowed the efficient synthesis of key bioactive stilbenes.

Impact of Design of Experiments in the Optimisation of Catalytic Reactions in Academia

“…New Heck-Matsuda conditions were tested using several styrenes (e.g., 7) and aryldiazonium tetrafluoroborates (e.g., 6), synthesising the desired stilbenes in good to high yields and selectivities while minimizing the use of benzonitrile as the solvent or co-solvent. 17 The protocol reported makes use of very practical, economical, and effective conditions. Correia et al started exploring the desired reactivity with few preliminary analyses concerning the effect of the solvents on the arylation.…”

Synthesis of Pterostilbene through supported-catalyst promoted Mizoroki-Heck reaction, and its transposition in continuous flow reactor

“…22 Correia et al, instead used an Heck-Matsuda coupling with arenediazonium salts instead of aryl halides and triflates, obtaining a really good yield (85%). 23 In a very recent interesting example, reported by Barlow et al Pterostilbene and other unsymmetrical stilbenes were synthesized by sequential Heck reactions of aryl bromides with ethylene. 24 Despite the important pharmacological properties of Pterostilbene and the several strategies described above, to obtain this molecule, as far as we know, there are still no studies with supported catalysts, neither on its transposition on continues flow reactors, with the aim to reach a more sustainable and green process.…”

Enzymatic Synthesis of Resveratrol α-Glycosides from β-Cyclodextrin-Resveratrol Complex in Water

“…Moreover, in the case of F. japonica , the level of piceid ( trans -3,5,4- O -trihydroxylstilbene-3-mono-β- d -glycoside) is 5–8 times greater than the level of trans -resveratrol that implies to hydrolyze piceid to increase the output of resveratrol. To overcome this drawback, a few chemical routes have been designed to access synthetic resveratrol at the multigram scale using cross metathesis coupling, Horner-Emmons olefination, as well as palladium-catalyzed Heck-Matsuda coupling reaction . Although these synthetic pathways provide resveratrol in good yields, they all involve a large number of steps and use rather toxic solvents/reagents.…”

“…To overcome this drawback, a few chemical routes have been designed to access synthetic resveratrol at the multigram scale using cross metathesis coupling, 8 Horner-Emmons olefination, 9 as well as palladiumcatalyzed Heck-Matsuda coupling reaction. 10 Although these synthetic pathways provide resveratrol in good yields, they all involve a large number of steps and use rather toxic solvents/ reagents. A more sustainable approach consists in producing resveratrol through vine cell culture.…”