Catalyse asymétrique de la réaction de type oxa-Michaël intramoléculaire

Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

The palladium-catalyzed cross-coupling reactions of 3-chloro-4-halogeno-1,2,5-thiadiazoles

3,4-Dichloro- and 3-chloro-4-halogeno-1,2,5-thiadiazoles (halogeno-: bromo- and iodo-) are involved in Pd-catalyzed cross-coupling reactions under Stille and Suzuki conditions. As a result, by using the commercially available 3,4-dichloro-1,2,5-thiadiazole as substrate, several 3-alkyl-, 3-alkenyl-, 3-alkynyl-and 3-aryl-4-chloro-1,2,5-thiadiazoles can easily be prepared. However, these reactions through direct desymmetrization of the 3,4-dichloro-1,2,5-thiadiazole always occur with side-reactions resulting from the concurrent decomposition of the heterocyclic ring of the starting material. These problems are resolved by involving, in these Pd-catalyzed cross-coupling reactions, the more reactive and selective 3-bromo-4-chloro- and 3-chloro-4-iodo-1,2,5-thiadiazole. These new dihalogeno-1,2,5-thiadiazoles can easily be prepared, via diazotization reaction followed by halogen substitution, from the 3-amino-4-chloro-1,2,5-thiadiazole

The Palladium-Catalyzed Cross-Coupling Reactions of 3-Chloro-4-halogeno-1,2,5-thiadiazoles.

3,4-Dichloro- and 3-chloro-4-halogeno-1,2,5-thiadiazoles (halogeno-: bromo- and iodo-) are involved in Pd-catalyzed cross-coupling reactions under Stille and Suzuki conditions. As a result, by using the commercially available 3,4-dichloro-1,2,5-thiadiazole as substrate, several 3-alkyl-, 3-alkenyl-, 3-alkynyl-and 3-aryl-4-chloro-1,2,5-thiadiazoles can easily be prepared. However, these reactions through direct desymmetrization of the 3,4-dichloro-1,2,5-thiadiazole always occur with side-reactions resulting from the concurrent decomposition of the heterocyclic ring of the starting material. These problems are resolved by involving, in these Pd-catalyzed cross-coupling reactions, the more reactive and selective 3-bromo-4-chloro- and 3-chloro-4-iodo-1,2,5-thiadiazole. These new dihalogeno-1,2,5-thiadiazoles can easily be prepared, via diazotization reaction followed by halogen substitution, from the 3-amino-4-chloro-1,2,5-thiadiazole

An organic solvent free process for the demethylation of 4-(4-methoxyphenyl)butanoic acid

A mild and efficient organic solvent free process has been developed for the synthesis of 4-(4-hydroxyphenyl)butanoic acid, a key intermediate in the synthesis of LY518674. Thus we have achieved the demethylation of 4-(4-methoxyphenyl)butanoic acid with only a slight excess of aqueous HBr and without phase transfer catalysis. In addition, 4-(4-hydroxyphenyl)butanoic acid is easily obtained by direct crystallization from the reaction mixture

Synthesis of 4,4 '-disubstituted azepines via ring-closing metathesis reaction and asymmetric arylation of lactones

The syntheses of the title compounds were accomplished via ail original sequence of reactions including the ring-closing metathesis of co-dienes by using the second-generation Grubbs' catalyst. The chiral diene precursors are available in racemic or optically enriched form from the corresponding alpha,alpha'-disubstituted lactones derivatives

A short and efficient synthesis of (R,R)-2-methylcyclopropanecarboxylic acid

We report herein a short and efficient synthesis of (RR)-2methyleyclopropanecarboxylic acid via a Horner-Wadsworth-Emmons reaction involving commercially available (S)-propylene oxide and triethylphosphonoacetate (TEPA). The TEPA/ base/propylene oxide stoichiometry was found critical to achieve high yields. We therefore studied the TEPA anion formation and stability using in situ IR spectroscopy. The reaction yield is strongly influenced by the counterion and solvent, whereas high diastereoselectivities are always obtained. Under the best experimental conditions (HexLi/MeTHF/150 degrees C), crude (RR)2-methylcyclopropanecarboxylic acid is obtained in 85-90% yield with > 98% trans selectivity

Mild and safer preparative method for nonsymmetrical sulfamides via N-sulfamoyloxazolidinone derivatives: Electronic effects affect the transsulfamoylation reactivity

Sulfamides (R1R2N-SO2-NR3R4) are traditionally prepared by using strong electrophilic and hazardous reagents such as N-sulfamoyl chloride, sulfonyl chloride, phosphorus oxychloride, or phosphorus pentachloride. We report here a safer and more convenient synthetic methodology for large-scale preparation of sulfamides using the N-substituted oxazolidin-2-one derivatives 5 as synthetic equivalent of the corrosive and hazardous N-sulfamoyl chloride. The scope of the use of N-sulfamoyloxazolidinones to prepare nonsymmetrical sulfamides is explored

Removal of reaction solvent by extractive workup: Survey of water and solvent co-extraction in various systems

In some chemical processes, extractive workup is used to remove the solvent of reaction in an aqueous layer and to isolate the product in the organic layer. Most of the time some reaction solvent is co-extracted in the organic layer, along with some water. This has a non-negligible impact on subsequent operations (washing, crystallization), and we have thus determined those levels for ten reaction solvents and five extraction solvents in order to help the process chemist in the development of efficient isolation procedures

Mechanistic insight into the (NHC)copper(I)-catalyzed hydrosilylation of ketones

(NHC)copper(I) hydride catalyzed ketone hydrosilylation is an efficient method for the enantioselective synthesis of secondary alcohols. Herein, we represent a computational study of this reaction using density functional theory (DFT) on realistic model systems. This study is supported by kinetic investigations, using in situ FTIR measurements. The calculations validate the previously proposed reaction mechanism and explain the high activity of (OR 1)xR2 3-xSi-H types of silanes. Experimental evidence in favor of the monomeric (NHC)CuH form of the catalyst is also given. Combining experimental and theoretical results furthermore highlights a Lewis base activation of the hydrosilane, leading to a modified suggestion for the mechanistic scheme of the catalytic cycle. © 2014 American Chemical Society