Michel Vaultier

Reduction d'azides en amines primaires par une methode generale utilisant la reaction de staudinger

Abstract A general chemoselective method for the reduction of azides into primary amines is described.

Over-stabilization of Candida antarctica lipase B by ionic liquids in ester synthesis

Four different ionic liquids, based on dialkylimidazolium cations associated with perfluorinated and bis(trifluoromethyl)sulfonyl amide anions were used as reaction media for butyl butyrate synthesis catalyzed by free Candida antarctica lipase B at 2% (v/v) water content and 50 °C. Lipase had enhanced synthetic activity in all ionic liquids in comparison with two organic solvents (hexane, and 1-butanol), the enhanced activity being related to the increase in polarity of ionic liquids. The continuous operation of lipase with all the assayed ionic liquids showed over-stabilization of the enzyme. The reuse of free lipase in 1-butyl-3-methylimidazolium hexafluorophosphate in continuous operation cycles showed a half-life time 2300 times greater than that observed when the enzyme was incubated in the absence of substrate (3.2 h), and a selectivity higher than 90%.

Criteria to Design Green Enzymatic Processes in Ionic Liquid/Supercritical Carbon Dioxide Systems

Five different ionic liquids (ILs) based on quaternary ammonium cations, with functional side chains ((3‐hydroxypropyl)‐trimethyl‐, (3‐cyanopropyl)‐trimethyl‐, butyl‐trimethyl‐, (5‐cyanopentyl)‐trimethyl‐ and hexyl‐trimethyl‐) associated with the same anion (bis(trifluoromethane)sulfonyl amide)), were synthesized, and their suitability for Candida antarctica lipase B (CALB)‐catalyzed ester synthesis in IL/supercritical carbon dioxide (scCO2) biphasic systems was assayed. Catalytic efficiency of the system has been analyzed as a function of both enzyme properties and mass‐transfer phenomena criteria. First, the suitability of these ILs as enzymic reaction media was tested for the kinetic resolution of rac‐phenylethanol. All ILs were found to be suitable media for enzyme catalysis, the best catalytic parameter (5.3 U/mg specific activity, 94.9% selectivity) being obtained for the (5‐cyanopentyl)‐trimethylammonium. Second, enzyme stability in all of the ILs was studied at 50 °C over a period of 50 days, and data were analyzed by a two‐step kinetic deactivation model. All of the ILs were shown to act as stabilizing agents with respect to hexane, producing an increase in the free energy of deactivation (to 25 kJ/mol protein) and an improvement in the half‐life time of the enzyme (2000‐fold), which agrees with the observed increased hydrophobicity of the cation alkyl side chain (measured by Hansenapos;s solubility parameter, δ). By using two different CALB‐IL systems with different hydrophobicity in the cation, continuous processes to synthesize six different short chain alkyl esters (butyl acetate, butyl propionate, butyl butyrate, hexyl propionate, hexyl butyrate, and octyl propionate) in scCO2 at 10 MPa and 50 °C were carried out. Both rate‐limiting parameters (synthetic activity and scCO2–ILs mass‐transfer phenomena) were related with the δ‐parameter of the ILs‐alkyl chain and reagents.

Lipase Catalysis in Ionic Liquids and Supercritical Carbon Dioxide at 150 °C

Free and immobilized Candida antarctica lipase B dispersed in ionic liquids (1‐ethyl‐3‐methylimidazolium bistriflimide and 1‐buthyl‐3‐methylimidazolium bistriflimide) were used as catalyst for the continuous kinetic resolution of rac‐1‐phenylethanol in supercritical carbon dioxide at 120 and 150 °C and 10 MPa. Excellent activity, stability and enantioselectivity levels were recorded in continuous operation.

On the nature of ionic liquids and their effects on lipases that catalyze ester synthesis

Free and immobilized lipases from Candida antarctica (CALA and CALB), Thermomyces lanuginosus (TLL) and Rhizomucor miehei (RML) were used as catalysts in the synthesis of butyl propionate by transesterification in reaction media consisting in nine different ionic liquids. Enzyme activities were clearly dependent on the nature of the ions, the results being improving as the alkyl chain length of the imidazolium cation increased, and as a function of the type of anion ([PF(6)], [BF(4)] or [ethylsulphate]). The best synthetic activity (655.5U/mg protein at 40 degrees C) was obtained when free CALB were assayed in the water-miscible IL cocosalkyl pentaethoxy methyl ammonium methosulfate ([CPMA][MS]), and was clearly related with the water content of the medium. The synthetic activity of free CALB in [CPMA][MS] was enhanced with the increase in temperature, while practically no effect was obtained for TLL. The ability of free CALB to synthesize aliphatic esters of different alkyl chain lengths, using different alkyl vinyl esters and 1-alkanols as substrates, was also studied in [CPMA][MS], the best results (4500U/mg protein) being obtained for the synthesis of hexyl butyrate.

Continuous green biocatalytic processes using ionic liquids and supercritical carbon dioxide

Soluble Candida antarctica lipase B dissolved in ionic liquids showed good synthetic activity, enantioselectivity and operational stability in supercritical carbon dioxide for both butyl butyrate synthesis and the kinetic resolution of 1-phenylethanol processes by transesterification.

Suzuki-type cross coupling reactions using palladium-water soluble catalyst. Synthesis of functionalized dienes

Abstract The palladium(0) catalyzed cross-coupling of boronic acids or esters conducted with a water soluble catalyst in the presence of organic base allows under mild condition the production of functionalized dienes. (60–90% yield).

Diels-Alder reactions of 1,3-dienylboronates as a new route to functionalized carbocycles.

Abstract Hydroboration of enynes with various hydroborating agents followed by refunctionalization at boron furnished 1,3-dienylboronates which undergo clean Diels-Alder addition to typical dienophiles. The resulting adducts contain an allylboronate functionality. Accordingly they add to aldehydes in a highly stereoselective fashion establishing the relative configuration at up to four stereogenic centers.

Dynamic structure–function relationships in enzyme stabilization by ionic liquids

The stability of α-chymotrypsin and Candida antarctica lipase B (CALB) in two ionic liquids (i.e. 1-ethyl-3-methyl-imidazolium, bis[(trifluoromethyl)sulfonyl]imide [emim] [NTf2], and butyl-trimethylamonium bis[(trifluoromethyl)sulfonyl]imide [btma] [NTf2]) has been studied. Both enzymes were strongly stabilized by the ionic liquids, the respective half-life times increasing 96 and 1660 times, with respect to those obtained in classical organic solvents such as 1-propanol and hexane, respectively. The stabilization of both enzymes by ionic liquids may be related to the associated structural changes of proteins that they can be observed by both fluorescence and circular dichroism spectroscopic studies.

Enantioselective cyclopropanation reactions in ionic liquids

Abstract The benchmark enantioselective cyclopropanation of styrene with ethyl diazoacetate, promoted by two different bis(oxazoline)-copper complexes, is studied in three ionic liquids. The nature of both the anion and cation influence the behaviour of the catalysts, which can be recovered and re-used.