Publications by authors named "Jean-Philippe Bouillon"

Catalytic hydrosilylation of 1,1-disubstituted enamides is one of the most challenging and synthetically useful processes in organosilicon chemistry and asymmetric catalysis. Herein, we report a rhodium-catalyzed enantioselective hydrosilylation of α-arylenamides with substituted hydrosilanes with the aid of chiral P-ligand, including newly developed spirophosphite ligands, giving various chiral β-silylated amides in excellent yields with good to excellent enantioselectivities (98:2 er after recrystallization). In addition, chiral β-silylated amines can be obtained by further functionalization of the hydrosilylation product.

View Article and Find Full Text PDF

We report a rhodium-catalyzed anti-Markovnikov regioselective hydrosilylation of trifluoromethylalkenes with substituted silanes giving various α-trifluoromethyl-β-silanes in good to excellent yields. The hydrogenation products were obtained via the same key intermediate treated with methanol as a protic solvent. Both transformations had a broad functional tolerance and were expected to facilitate the construction of complex α-trifluoromethyl compounds.

View Article and Find Full Text PDF

-Bromofluoroalkenes have been combined with phosphite under irradiation, in the presence of Fukuzumi's catalyst (9-mesityl-10-methylacridinium perchlorate) as an organic photocatalyst, to provide valuable -fluorophosphonate derivatives, known as stable mimics of phosphates. The desired products were obtained in good to excellent yields, and the reaction showed very good chemical tolerance.

View Article and Find Full Text PDF

A series of ferrocenyl-containing γ-hydroxy-γ-lactam tetramates were prepared in 2-3 steps through ring opening-ring closure (RORC) process of γ-ylidene-tetronate derivatives in the presence of ferrocenyl alkylamines. The compounds were screened in vitro for their antiplasmodial activity against chloroquine-sensitive (3D7) and chloroquine-resistant (W2) clones of P. falciparum, displaying activity in the range of 0.

View Article and Find Full Text PDF

The catalytic asymmetric synthesis of highly functionalized cyclopropanes from α-substituted allyl sulfones and silanes is reported. The reaction, using α-aryl diazoacetates or diacceptor diazo reagents, catalyzed by a chiral rhodium complex (Rh ((S)-BTPCP) ), furnished the corresponding cyclopropanes in moderate to high yields (27-97 %), high diastereoselectivities (68 : 32 to 20 : 1 d.r.

View Article and Find Full Text PDF

gem-Heteroatom-substituted fluoroalkenes have received little attention despite their great potential in medicinal chemistry or in fine chemistry. Indeed, due to the electronic and steric similarity between the fluoroalkene moiety and the amide bond as well as the high strength of the carbon-fluorine bond, these gem-heteroatom-substituted fluoroalkenes could be envisioned as stable mimics of various important organic functions, such as phosphates, carbamates, S-thiocarbamates and ureas. We present herein an overview describing the syntheses over the last decade of heteroatom-substituted fluoroalkenes in geminal position.

View Article and Find Full Text PDF

The photocatalytic contra-thermodynamic E→Z isomerization of vinyl boronates by using a binaphthol catalyst is disclosed. The reaction, based on the transient formation of a suitable chromophore with a BINOL derivative as the catalyst, allowed geometrical isomerization in good-to-excellent Z/E ratio and excellent-to-quantitative yields. The mechanism of this E→Z contra-thermodynamic isomerization was studied, and the formation of a transient chromophore species is suggested.

View Article and Find Full Text PDF

Decarboxylation strategy has been emerging as a powerful tool for the synthesis of fluorine-containing organic compounds that play important roles in various fields such as pharmaceuticals, agrochemicals, and materials science. Considerable progress in decarboxylation has been made over the past decade towards the construction of diverse valuable fluorinated fine chemicals for which the fluorinated part can be brought in two ways. The first way is described as the reaction of non-fluorinated carboxylic acids (and their derivatives) with fluorinating reagents, as well as fluorine-containing building blocks.

View Article and Find Full Text PDF

The -thermodynamic isomerization of α- and β-substituted cinnamate derivatives catalyzed by the Cu(OAc)/-BINAP complex under blue light irradiation is reported. The use of an oxazolidinone template, which favored the complexation of the copper catalyst to the substrate, allowed the → isomerization of the catalytically formed chromophore under simple and robust reaction conditions in good to excellent ratios. The mechanism of this process based on the transient formation of a chromophore was also studied.

View Article and Find Full Text PDF

We report here a simple and robust gold-catalyzed annulation reaction, giving - and -spirocycles in good to excellent yields. We have prepared a library of protected amines and tertiary alcohols that give, upon cyclization with alkynes, a representative set of heterospirocycles and illustrate reaction compatibility with diverse functional groups. A change in catalytic activity is possible by modifying the solvent, and two original tricyclic spirocycles were synthesized in a tandem reaction.

View Article and Find Full Text PDF

A series of iodinated ligands for the SPECT imaging of 5-HT receptors was designed starting from the previously reported hit MR-26132. We focused on the modulation of the piperidine-containing lateral chain by introducing hydrophilic groups in order to decrease the liphophilicity of the new ligands. All the synthesized compounds were tested for their binding affinities on 5-HTRs and based on the Ligand Lipophilicity Efficiency approach, compound 13 was further selected for radioiodination with iodine-125 and imaging experiments.

View Article and Find Full Text PDF

Efficient ligand-free palladium catalyzed Mizoroki-Heck reaction allowed the formation of trisubstituted α-trifluoromethylacrylates. The reaction showed good chemical tolerance and furnished moderate to excellent yields of reaction. Silver salt additive proved to be essential for the reaction.

View Article and Find Full Text PDF

The palladium-mediated C-H radio-iodination of arenes using sodium iodide as the primary isotopic source is reported and performed without chemical know-how in 30 min and applied to the synthesis of complex radio-iodinated compounds of biological interest.

View Article and Find Full Text PDF

The first catalytic asymmetric synthesis of highly functionalized pentafluorosulfanylated pyrrolidines is described. The method, based on a 1,3-dipolar cycloaddition reaction of aryl and heteroaryl-substituted glycine Schiff bases with pentafluorosulfanyl acrylic esters, gave access to a broad range of pyrrolidines bearing aryl, naphtyl, and heteroaryl groups. By using Xing-Phos as a catalyst, the corresponding products were obtained in good yields, good to high regioselectivity, and excellent diastereo- and enantioselectivities (up to 98 % ee).

View Article and Find Full Text PDF

Cyclic nucleotide phosphodiesterase type 4 (PDE4), that controls intracellular level of cyclic nucleotide cAMP, has aroused scientific attention as a suitable target for anti-inflammatory therapy in respiratory diseases. Here we describe the development of two families of pyridazinone derivatives as potential PDE4 inhibitors and their evaluation as anti-inflammatory agents. Among these derivatives, 4,5-dihydropyridazinone representatives possess promising activity, selectivity towards PDE4 isoenzymes and are able to reduce IL-8 production by human primary polymorphonuclear cells.

View Article and Find Full Text PDF

The Pd-catalyzed diastereoselective trifluoromethylthiolation of acrylamides was developed to allow the formation of the Z-isomer as a single product. Using a C-H bond functionalization strategy, the method was applied to a broad range of α-aryl, α-alkyl, and α,β-disubstituted acrylamides bearing the amide derived from the 8-aminoquinoline as a directing group. Mechanistic studies as well as postfunctionalization of the products were performed.

View Article and Find Full Text PDF

A palladium-catalyzed C-H bond functionalization of acrylamides was developed to build up stereoselectively trifluoromethylated 1,3-butadienes. Using a tertiary amide as a directing group, olefins were selectively functionalized with 2-bromo-3,3,3-trifluoropropene to access these important fluorinated compounds. The methodology was extended to the construction of pentafluoroethyl-substituted 1,3-dienes.

View Article and Find Full Text PDF

This work describes the first transition metal-free stereospecific synthesis of (E)-(1-fluoro-2-arylvinyl)phosphine boranes through the addition of diarylphosphine-boranes to gem-bromofluoroalkenes in the presence of a base at room temperature. The reaction proceeds well under very mild conditions and tolerates a variety of functionalities. Scope and limitations of the reaction are discussed.

View Article and Find Full Text PDF

In this Letter we report on an efficient and short 2-3 steps synthesis of γ-hydroxy-γ-lactam derived-tetramates bearing a 7-chloro-4-aminoquinoline skeleton and their evaluation as potent antimalarials. These molecules were obtained through ring opening-ring closure (RORC) process of γ-ylidene-tetronate derivatives in the presence of 7-chloro-4-aminoquinoline-derived amines. In vitro antimalarial activity of these new γ-lactams was evaluated against Plasmodium falciparum clones of variable sensitivity (3D7 and W2) and they were found to be active in the range of 14-827nM with generally good resistance index.

View Article and Find Full Text PDF

Ligand-free, efficient, palladium-catalyzed Mizoroki-Heck reaction between methyl α-fluoroacrylate and arene or hetarene iodides is reported for the first time. The reaction is stereospecific and provides fair to quantitative yields of fluoroalkenes. The Mizoroki-Heck reaction starting from more hindered and usually reluctant trisubstituted acrylate, to access tetrasubstituted fluoroalkenes, is also reported.

View Article and Find Full Text PDF

Copper-catalyzed direct C-H fluoroalkenylation of heterocycles using various gem-bromofluoroalkenes as electrophiles is reported. This efficient method offers step-economical, low-cost and stereocontrolled access to relevant heteroarylated monofluoroalkenes. The synthesis of fluorinated analogues of biomolecules and therapeutic agents for the treatment of Duchenne muscular dystrophy as application is reported.

View Article and Find Full Text PDF

With the aim to develop a suitable radiotracer for the brain imaging of the serotonin 4 receptor subtype (5-HT4R) using single photon emission computed tomography (SPECT), we synthesized and evaluated a library of di- and triazaphenanthridines with lipophilicity values which were in the range expected to favour brain penetration, and which demonstrated specific binding to the target of interest. Adding additional nitrogen atoms to previously described phenanthridine ligands exhibiting a high unspecific binding, we were able to design a radioiodinated compound [(125)I]14. This compound exhibited a binding affinity value of 0.

View Article and Find Full Text PDF

In this Letter we report on a multi-step synthesis of 5-((arylthio- and heteroarylthio)-methylene)-3-(2,2,2-trifluoroethyl)furan-2(5H)-ones starting from γ-keto thiolester or γ-keto carboxylic acid. The key intermediate γ-lactones were then reacted with 4-aminoquinoline-derived amines via ring opening-ring closure (RORC) process affording the corresponding γ-hydroxy-γ-lactams in moderate to good yields. In vitro antimalarial activity of the resulting new 4-aminoquinoline γ-lactams were evaluated against Plasmodium falciparum clones of variable sensitivity (3D7 and W2) and were found to be active in the range of 89-1600 nM with good resistance index and did not show cytotoxicity in vitro when tested against human umbilical vein endothelial cells (HUVEC) up to concentration of 50 μM.

View Article and Find Full Text PDF

Original mixed selectors were synthesized by coupling a single L-valine diamide moiety on permethylated β-cyclodextrin. The structures of the new selectors were designed to limit the interactions between the L-valine derivative and cyclodextrin by removing the amino acid moiety from the cyclodextrin cavity by means of an amide linkage on mono-6-amino permethylated β-CD or the insertion of a carboxymethyl group. The accessibility of the amino acid group moiety was thus facilitated.

View Article and Find Full Text PDF

In this paper we report the synthesis and antimalarial properties of two series of fluoroalkylated γ-lactams derived from 4-aminoquinoline as potent chemotherapeutic agents for malaria treatment. These molecules obtained in several steps resulted in the identification of very potent structures with in vitro activity against Plasmodium falciparum clones of variable sensitivity (3D7 and W2) in the range of 19-50 nM with resistance indices in the range of 1.0-2.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_sessioni28f78k0nr6lkogm3rat4rm8m18pnflt): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once