Hamed Ben Ammar

Eco‐Friendly Solvents for Palladium‐Catalyzed Desulfitative CH Bond Arylation of Heteroarenes

Herein, we report the Pd-catalyzed regioselective direct arylation of heteroarenes in which benzenesulfonyl chlorides are used as coupling partners through a desulfitative cross-coupling that can be performed in diethyl carbonate (DEC) or cyclopentyl methyl ether (CPME) as green and renewable solvents or even in neat conditions instead of dioxane or dimethylacetamide (DMA). Under these solvent conditions, the reaction proceeds with a wide range of heteroarenes. C2- or C5-arylated products were obtained with furan and pyrrole derivatives. Benzofuran was also arylated regioselectively at the C2-position, whereas the reaction proceeds selectively at the C3- or C4-positions if thiophenes and benzothiophenes are used. Moreover, in some cases, especially with 1-methylindole, solvent-free conditions afforded better regioselectivities and/or yields than the reaction performed in the presence of solvents.

Conditions for palladium-catalyzed direct arylations of 4-bromo and 4-iodo N -substituted pyrazoles without C–Br or C–I bond cleavage

The Pd-catalyzed arylation at the C5 position of N-protected pyrazole derivatives bearing bromo or iodo substituents at the C4 position is described. A simple phosphine-free catalytic system was used, namely, 1 mol% Pd(OAc)2 in DMA in the presence of KOAc as the base. A wide aryl bromide scope as a coupling partner has been coupled with pyrazole derivatives. The reaction was very chemoselective as the C–halogen bonds of the pyrazole units were not involved in the C–H bond arylation process. Some examples demonstrating the synthetic potential of the bromo and iodo pyrazole substituents for chemical transformations are reported.

Reactivity of bromofluorenes in palladium-catalysed direct arylation of heteroaromatics

The palladium-catalysed direct arylation using bromofluorenes and heteroaromatics as the coupling partners proceeded in moderate to high yields using only 0.1–0.5 mol% Pd(OAc)2 or 1 mol% PdCl(C3H5)(dppb) as the catalyst and KOAc as the base. A wide variety of heteroarenes have been successfully employed, allowing their properties to be easily tuned. From 2,7-dibromofluorene, successive arylations allow the introduction of two different heteroarenes at carbons C2 and C7.

New chiral 4-substituted 2-cyanoethyl-oxazolines: synthesis and assessment of some biological activities.

This paper describes the synthesis of new enantiomerically pure 2-cyanoethyl-oxazolines in one step starting from a wide range of amino alcohols and 4-ethoxy-4-iminobutanenitrile with high to good yields (73-96%) via an appropriate procedure which can be used for a selective synthesis of mono-oxazolines. A simple operation as well as a practical separation is additional eco-friendly attributes of this method. All the synthesized compounds were identified and characterized with their physicochemical features and their spectral data ((1)H NMR, (13)C NMR and TOFMS ES(+)). Among the prepared mono-oxazolines, the mono-oxazoline (3a) [3-[(4S)-4-benzyl-4,5-dihydro-1,3-oxazol-2-yl] propanenitrile] was tested to detect some biological activities. This compound was studied in vitro given the various types of pharmacological properties characterizing these compounds such as antioxidant, antimicrobial and analgesic activities. The antioxidant activity and mechanism of (3a) were identified using various in vitro antioxidant assays including 1,1-diphenyl-2-picryl-hydrazyl (DPPH), and superoxide anion radicals (O2(-)) scavenging activity. In addition, compared to Quercetin, the tested synthetic product reveals a relatively-strong antiradical activity towards the DPPH (activity percentage of 81.22%) free radicals and significantly decreased the reactive oxygen species such as (O2(-)) formation evaluated by the non-enzymatic (nitroblue tetrazolium/riboflavine) and the enzymatic (xanthine/xanthine oxidase) systems. Related activity values were, respectively, 66% and 60.30%. The oxazoline (3a) showed a high ability to reduce the O2(-) generation and proved to be a very potent radical scavenger. On the other hand, the analgesic property of the 3[(4S)-benzyl-4,5-dihydro-1,3-oxazol-2-yl] propanenitrile (3a) was demonstrated. The subcutaneous administration of (3a) produced a significant reduction in the number of abdominal constrictions amounting to 73.81% in the acetic acid writhing test in mice. In addition to these advances, the oxazoline (3a) has been investigated as an antimicrobial agent. Our results showed that this molecule exhibited various levels of antibacterial effect against all the tested bacterial strains.

Palladium-Catalyzed C–H Bond Functionalization of 6,6-Diphenylfulvenes: An Easier Access to C1-Arylated and C1,C4-Diarylated Fulvenes

Conditions allowing the palladium-catalyzed regioselective direct arylation of fulvene derivatives are reported. The nature of the aryl source exhibits an important influence on the yield. The reaction of fulvenes with aryl bromides gave poor yields, whereas the use of benzenesulfonyl chlorides gave rise to fulvenes arylated at C1- and C4-positions on the 5-membered ring in good yields. The reaction tolerates various substituents such as nitrile, nitro, fluoro, trifluoromethyl, chloro, or even bromo on the benzenesulfonyl chloride.

Regiocontroled Pd-catalysed C5-arylation of 3-substituted thiophene derivatives using a bromo-substituent as blocking group

Summary The use of a bromo-substituent as blocking group at the C2-position of 3-substituted thiophenes allows the regioselective introduction of aryl substituents at C5-position via Pd-catalysed direct arylation. With 1 mol % of a phosphine-free Pd catalyst, KOAc as the base and DMA as the solvent and various electron-deficient aryl bromides as aryl sources, C5-(hetero)arylated thiophenes were synthesized in moderate to high yields, without cleavage of the thienyl C–Br bond. Moreover, sequential direct thienyl C5-arylation followed by Pd-catalysed direct arylation or Suzuki coupling at the C2-position allows to prepare 2,5-di(hetero)arylated thiophenes bearing two different (hetero)aryl units in only two steps. This method provides a “green” access to arylated thiophene derivatives as it reduces the number of steps to prepare these compounds and also the formation of wastes.

3-Amino-4-(1,3-benzoxazol-2-yl)-5-(cyclo-hexyl-amino)-thio-phene-2-carbo-nitrile.

In the title compound, C18H18N4OS, the cyclohexyl ring adopts a chair conformation. The other rings of this compound lie almost in the same plane, with a mean deviation of 0.03 (2) Å from the least-squares plane defined by the 14 constituent atoms. There are intramolecular N—H⋯N and N—H⋯O hydrogen bonds, as well as intermolecular N—H⋯N hydrogen bonds, which link the molecules into centrosymmetric dimers.