An enhanced stereoselective synthesis of α,β-unsaturated esters through the Horner–Wadsworth–Emmons reaction in deep eutectic solvents

Paparella, Andrea Nicola; Stallone, Margherita; Pulpito, Mara; Perna, Filippo Maria; Capriati, Vito; Vitale, Paola

doi:10.1039/d3ob02083e

Cited by 4 publications

(1 citation statement)

References 38 publications

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“…R f : 0.33 (hexane/AcOEt 90:10 v/v). 1 H-NMR consistent with literature ( De Vries, 2018 ; Paparella et al, 2024 ) (see Supplementary Material ). HPLC (Method 2): tR = 17.0.…”

Section: Methodssupporting

confidence: 83%

A green Heck reaction protocol towards trisubstituted alkenes, versatile pharmaceutical intermediates

Rossino,

Marrubini,

Brindisi

et al. 2024

Front. Chem.

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The Heck reaction is widely employed to build a variety of biologically relevant scaffolds and has been successfully implemented in the production of active pharmaceutical ingredients (APIs). Typically, the reaction with terminal alkenes gives high yields and stereoselectivity toward the trans-substituted alkenes product, and many green variants of the original protocol have been developed for such substrates. However, these methodologies may not be applied with the same efficiency to reactions with challenging substrates, such as internal olefins, providing trisubstituted alkenes. In the present work, we have implemented a Heck reaction protocol under green conditions to access trisubstituted alkenes as final products or key intermediates of pharmaceutical interest. A set of preliminary experiments performed on a model reaction led to selecting a simple and green setup based on a design of experiments (DoE) study. In such a way, the best experimental conditions (catalyst loading, equivalents of alkene, base and tetraalkylammonium salt, composition, and amount of solvent) have been identified. Then, a second set of experiments were performed, bringing the reaction to completion and considering additional factors. The protocol thus defined involves using EtOH as the solvent, microwave (mw) irradiation to achieve short reaction times, and the supported catalyst Pd EnCat®40, which affords an easier recovery and reuse. These conditions were tested on different aryl bromides and internal olefines to evaluate the substrate scope. Furthermore, with the aim to limit as much as possible the production of waste, a simple isomerization procedure was developed to convert the isomeric byproducts into the desired conjugated E alkene, which is also the thermodynamically favoured product. The approach herein disclosed represents a green, efficient, and easy-to-use handle towards different trisubstituted alkenes via the Heck reaction.

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“…R f : 0.33 (hexane/AcOEt 90:10 v/v). 1 H-NMR consistent with literature ( De Vries, 2018 ; Paparella et al, 2024 ) (see Supplementary Material ). HPLC (Method 2): tR = 17.0.…”

Section: Methodssupporting

confidence: 83%

A green Heck reaction protocol towards trisubstituted alkenes, versatile pharmaceutical intermediates

Rossino,

Marrubini,

Brindisi

et al. 2024

Front. Chem.

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Wittig Reaction in Deep Eutectic Solvents: Expanding the DES Toolbox in Synthesis

De Nardi,

Gorreta,

Meazzo

et al. 2024

Chemistry A European J

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Wittig reaction between substituted phosphonium salts and (hetero)aromatic and alkyl carbonyl compounds in Deep Eutectic Solvents has been developed under a scalable and friendly protocol. Highly efficient reactions were successfully run with a wide range of bases including organic (DBU, LiTMP, t‐BuOK) and inorganic (NaOH, Na2CO3, K2CO3) ones in ChCl/Gly 1:2 (mol/mol) as solvent under mild conditions, at room temperature and under air. The proposed protocol was applied to a wide range of substrates, including (hetero)aromatic aldehydes with substituents as halogens (I, Br, Cl), EDG (alkoxy, methyl), EWG (NO2, CF3) or reactive groups as CN, esters, and ketones. Vinylic, alkynyl and cycloalkyl, alicyclic and α,β‐unsaturated aldehydes can also be used. Highly electrophilic ketones gave good yields. The diastereoselectivity of the reaction is in complete agreement with the E/Z ratio observed under traditional conditions. We demonstrated that the reaction is scalable to 2 g (5 mmol) of phosphonium salt, furthermore the proposed workup protocol allows to remove TPPO without need of additional chromatographic purification.

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Selective and fast oxidation of alcohol to aldehyde using novel catalytic deep eutectic solvent surfactants

Shokr Chalaki,

Azizi,

Mirjafary

et al. 2024

Front. Chem.

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Deep eutectic solvent (DES) has been considered as a useful catalyst and reaction medium for various organic transformations. Herein, we report the catalytic application of novel deep eutectic solvent- based surfactant (DES surfactant) for the selective and fast oxidation of alcohols to aldehydes. The readily accessible DES surfactants (FeCl3/BHDC) was prepared using inexpensive ferric chloride (FeCl3) and benzyl hexadecyl dimethyl ammonium chloride in a simple manner. The synthesized FeCl3/BHDC was characterized using various techniques, including, FTIR spectroscopy, thermal gravimetric analysis (TGA), scanning electron microscopy (SEM), and energy- dispersive X-ray spectroscopy (EDS) to determine its structure. The catalytic activity of FeCl3/BHDC in the selective oxidation of various alcohols to corresponding aldehyde derivative was investigated. The results showed the reaction could be completed within very short reaction times ranging from 2 to 15 min, while achieving good to excellent yields. This protocol offers a facile strategy and excellent efficiency in selectively oxidizing various alcohol derivatives to their respective aldehydes and ketones, utilizing hydrogen peroxide in the presence of catalytic DES surfactant.

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An enhanced stereoselective synthesis of α,β-unsaturated esters through the Horner–Wadsworth–Emmons reaction in deep eutectic solvents

Abstract: A new scalable synthesis of (E)-α,β-unsaturated esters has been developed using protic, non-toxic, and biodegradable Deep Eutectic Solvents through the Horner-Wadsworth-Emmons reaction between triethyl phosphonates and (hetero)aromatic carbonyl compounds, encompassing...

Cited by 4 publications

References 38 publications

A green Heck reaction protocol towards trisubstituted alkenes, versatile pharmaceutical intermediates

A green Heck reaction protocol towards trisubstituted alkenes, versatile pharmaceutical intermediates

Wittig Reaction in Deep Eutectic Solvents: Expanding the DES Toolbox in Synthesis

Selective and fast oxidation of alcohol to aldehyde using novel catalytic deep eutectic solvent surfactants

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