Raouf Echarri

Synthesis of 2-deoxy-3,5-di-O-benzoyl-2,2-difluoro-D-ribose from D-glucose and D-mannose. A formal synthesis of gemcitabine

Abstract The title compound 2-Deoxy-3,5-di-O-benzoyl-2,2-difluoro-D-ribose (17), was synthesised from D-glucose and from D-mannose. The key steps of the synthesis from D-glucose are obtaining the 3,3-difluoropyranose 9 by reacting the ulose 7 with DAST, and their conversion into the difluorofuranoside 17 by a degradative reaction of diol 16. Starting from D-mannose the synthesis obtains the 3,3-difluoroglycal 22 by reaction of the ulose 18 with DAST and oxidation-elimination of selenoglycoside 21. Ozonolysis of 22 gives the difluorofuranose 17.

The reaction of pyranoside 2-uloses with DAST revised. Synthesis of 1-fluoro-ketofuranosyl fluorides and their reactivity with alcohols

Abstract We have reinvestigated the reaction of α-pyranosides-2-uloses 13 , 14 , 19 and 24 with DAST and shown that the 1,2-difluorinated compounds 17 , 18 and 25 are produced by a ring-contraction reaction. The reaction of 18 with benzyl alcohol gives the tri-benzyl derivative 26 or compound 27 , depending on the reaction conditions. Treating 17 with 2-naphthol produced the spiranic compounds 29 – 31 . The reaction of 17 with bis(trimethylsilyl)uracil produced the mononucleoside 28 , which preserves the fluorine atom in the more substituted carbon.

Synthesis of isochromane derivatives by metallocene-promoted reaction of 2-alkoxy-2-fluoro-glycosyl fluorides with benzyl alcohol

Abstract Isochromane derivatives have been obtained by reaction of glycosyl fluorides with benzyl alcohol in presence of Cp2HfCl2/ AgClO4, by a glycosylation, migration, and intramolecular cyclization sequence.

RHODIUM CATIONIC COMPLEXES USING DITHIOETHERS AS CHIRAL LIGANDS. APPLICATION IN STYRENE HYDROFORMYLATION

Addition of the dithioethers (−)-DIOSR2 (R=Me, iPr) (2,3-O-isopropylidene-1,4-dimethyl (and diisopropyl) thioether-L-threitol) to a dichloromethane solution of [Rh(COD)2]ClO4 (COD=1,5-cyclooctadiene) yielded the mononuclear complexes [Rh(COD)(DIOSR2)]ClO4. X-ray diffraction methods showed that the [Rh(COD)(DIOSiPr2)]ClO4 complex had an square-planar coordination geometry at the rhodium atom with the iPr groups in anti position. Cyclooctadiene complexes react with carbon monoxide to form dinuclear tetracarbonylated complexes [(CO)2Rh(μ-DIOSR2)2(CO)2](ClO4)2. [Rh(COD)(DIOSR2)]ClO4 are active catalyst precursors in styrene hydroformylation at 30 atm and 65°C which give conversions of up to 99% with a regioselectivity in 2-phenylpropanal as high as 74%. In all cases enantioselectivities are low.

Stereoselective synthesis of nucleosides by metallocene-promoted activation of glycosyl fluorides

Abstract The Cp 2 MCl 2 -AgX (M=Hf, Zr; X=ClO 4 , OTf) mixture is very effective for the promotion of the coupling of glycosyl fluorides and bis(trimethylsilyl)uracil. The stereoselectivity of the reaction depends on the solvent employed. Application to the synthesis of 1-(3,4 -isopropylidene-2-fluoro-2-O-methyl-α-D-ribopentopyranosyl)uracil is described.

New camphor-derived sulfur chiral controllers: Synthesis of (2R-exo)-10-methylthio-2-bornanethiol and (2R-exo)-2,10-bis(methylthio)bornane

Abstract An efficient preparation of two camphor-derived controllers [(2R-exo)-10-methylthio-2-bornanethiol1b and (2R-exo)-2,10-bis(methylthio)bornane 2] potentially useful as a ligands or chiral auxiliaries in asymmetric synthesis is described. Both compounds have been prepared starting from (1S)-camphor-10-thiol 3. Alkylation of this thiol with sodium methoxide and methyl iodide afforded 10-methylthiocamphor 8. Conversion of 8 into the corresponding thioketone 9 with the Lawessons reagent followed by the stereoselective reduction with DIBAL-H at low temperature yielded (2R-exo)-10-methylthio-2-bornanethiol1b in good yield. (2R-exo)-2,10-bis(Methylthio)bornane 2 could be obtained by alkylation of 1b with sodium methoxide and methyl iodide.

2-Alkoxy-2-fluoro-glycosyl fluorides as 1,2-dielectrophilic synthons for the synthesis of naphtho- and benzo-dihydrofuran derivatives

Abstract Benzo and naphtho-dihydrofuran derivatives were obtained by the reaction of glycosyl fluorides with phenol and naphthol derivatives in the presence of Cp 2 MCl 2 AgOTf (M = Hf, Zr) . This process include a glycosylation, 1,2-migration and an intramolecular cyclization.

Isochromane versus O-glycoside synthesis : a study of the reaction of 2-alkoxy-2-fluoro-glycosyl fluorides with alcohols

Abstract 2-alkoxy-2-fluoro-glycosyl fluorides 1a and 1b react with benzyl alcohol derivatives in the presence of the fluorine activating system Cp2HfCl2/AgClO4 giving isochromane or O-glycosides derivatives depending on the glycosyl fluoride/alcohol ratio. A mechanism of the consecutive reactions leading to the isochromane derivatives is proposed.