Claude Beguin

Acide fluoro-2 phenyl-2 acetique: Synthesis, configuration absolute et emploi comme agent chiral de derivation

Abstract 2-Fluoro-2-phenyl acetic acid was synthetized from phenylglycine through a fluorodeamination reaction in a HF : pyridine mixture or from ethylmandelate through fluorodehydroxylation using the reagent fluoroamine (FAR). The specific rotation of S-2-fluoro-2-phenyl acetic acid is [α] 20D = + 153° in chloroform at concentration c = 1,25 g/100 ml. This acid can be used as a derivatizing chiral agent : the enantiomers can be distinguished and the enantiomeric excess of secondary alcohols can be determined by 19F NMR spectra of the corresponding esters.

New processes for the halofluorination of norbornadiene. Structural reexamination of the products. Evidence for exclusive exo attack by electrophiles

Abstract The bromofluorination of norbornadiene using NBS in the presence of the new fluorinating agent Et3N/3HF leads to a 3:2 mixture of 3-exo-bromo-5-exo-fluoronortricyclane 1 and 3-exo-bromo-5-endo-fluoronortricyclane 2 . The structures of these compounds were proven by independent syntheses and extensive NMR spectroscopic studies. The structure (3-endo-bromo-5-exo-fluoronortricyclane) given for the minor compound in the literature10 was revised especially in terms of the comparison of 3JCF coupling constants in the 13 C NMR spectra of both compounds. No evidence for an endo attack of the bromonium species on norbornadiene as stated in the literature10 was observed.

Synthesis of β-fluoroazides: a route to primary β-fluoro amines

Abstract Two ways for the synthesis of β-fluoroazides are presented. The first one uses 1,2,2-trifluoro-2-chloro triethylamine (FAR) as a fluorinating reagent on the corresponding azidoalcohols. It is a smooth reaction at room temperature, but is not stereospecific; it works well for phenyl substituted or primary α-carbon β-fluoroazides. The second route is the substitution of the azide group for bromine on an appropriate fluorobromide in phase transfer conditions. It is stereospecific (except for one case). It works well to give pure diastereoisomers of β-fluoroazides with pseudo primary (with deuterium) or secondary α-carbon atoms.

A new bacterial dehydrogenase oxidizing the lignin model compound guaiacylglycerol β-O-4-guaiacyl ether

A lignin model compound, named in short guaiagylglycerol beta-guaiacyl ether (GGE), contains the beta-0-4 ether linkage that is common in the chemical structure of lignin. A Pseudomonas sp. (GU5) had been isolated as an organism able to grow with GGE as the sole source of carbon and energy. When grown on vanillate, the bacteria contained a NAD+ -dependent dehydrogenase converting GGE to a 355 nm absorbing product. The enzyme, named GGE-dehydrogenase, was purified about 160-fold using gel permeation, ion exchange on DEAE-Sephadex, and dye-ligand affinity chromatography. The new protein was about 52 kDa in apparent size with but one polypeptide chain after denaturation and reduction. According to several criteria, the product of GGE oxidation (Km = 12 microM) was identified as the corresponding conjugated ketone at the alpha-carbon of the C3 side-chain. The secondary alcohol function in GGE was apparently the sole target of the enzyme action. However the conversion of GGE into ketone catalyzed by the enzyme was only partial, and did not exceed 50%, probably because only one of the alpha-enantiomers was susceptible to enzyme attack. In contrast the ketone, either made by organic synthesis or by enzymic oxidation of GGE, could be totally reduced back to GGE (Km = 13 microM at pH 8.4, 8 microM at neutral pH), with NADH as the reductant, as confirmed by UV absorption and NMR spectra. Other model compounds with no primary alcoholic function, ether linkage or phenolic group were also substrates for the enzyme, confirming the specificity of GGE-dehydrogenase for the alpha-carbon position. Conjugation of the alpha-ketone with an adjacent phenolic nucleus interfered strongly with equilibrium constants and redox potentials of the system according to pH, and the enzyme displayed widely different optima with pH over 9 when oxidizing GGE, below 7 when reducing the ketone. Equilibrium studies showed that the ketone/GGE potential was -0.37 volt at pH 8.7, -0.23 volt at pH 7 (30 degrees C). The significance of this new dehydrogenase and its properties are discussed, especially in the general concern of lignin biodegradation.

Synthese et stereochimie de formation d'amines tertiaires β-fluorees par fluoration d'aminoalcools avec la trifluro-1,1,2 chloro-2 N,N-diethyl ethylamine (FAR) et le melange HF - pyridine.

Abstract The fluorination of amino-alcohols giving tertiary β-fluoroamines was studied synthetically and stereochemically. Configuration of initial and final products were assigned using 1H and 19F NMR. The fluorination of amino-alcohols with FAR is a stereospecific reaction with retention of configuration. Isomerically or optically pure compounds can be obtained. The fluorination with HF - pyridine mixture gives preferentially threo fluoroamines.

Preferential conformation of the carbon-fluorine bond and electronic interactions in substituted benzyl fluorides

Abstract CNDO/2 and PCILO calculations have been used to study the preferential conformations and relative stabilities of six para-substituted, three ortho-substituted and two diortho-substituted benzyl fluorides. In non-ortho-substituted compounds, the C-F bond of the CH 2 F group lies preferentially in the plane of the phenyl ring. The HOMO energies show that conjugation exists between the substituent and the fluorine atom. Some experimental evidence has been obtained through the use of Raman spectroscopy on the crystalline state. For ortho-substituted compounds the calculations are in agreement with several previous studies which show that steric hindrance can lead to a change in the preferential conformation in the phenyl ring plane as occurs in 2,6-dichlorobenzyl fluoride.

Selective reduction of β-fluoroazides to β-fluoroamines

Abstract Three methods were tested to reduce chemoselectively β-fluoroazides into β-fluoroamines : catalytic hydrogenation, catalytic transfer hydrogenation, and reduction with triphenyl phosphine. The last was the best.

Equilibrium constants of HF, F-, HF-2 and H2F2 species in formic acid.

Abstract Equilibrium constants for the fluorinated species HF, F-, HF-2 and H2F2 in formic acid and in a 1M potassium formate solution in formic acid have been studied by 19F NMR. The chemical shifts of these species have been determined from measurements of the shifts for various initial mixtures of differing concentrations of dissolved HF, F- and HF-2. From these values, relative concentrations of HF, F-, and HF-2 and H2F2 in each solution have been calculated through a numerical method. The following constants were obtained: K1 = [H+][F-]/[HF] = 1.1 x 10-5M; KD = [HF][F-]/[HF-2] = 0.5 M; K′1 = [H+][HF-2]/[H2F2]= 1.1 x 10-5 M; K′D = [HF]2/[H2F2]=0.5 M.

NMR conformational investigation of stereocontrolled reduction of lignin-model compounds

The stereochemical pathway of the hybride reductions of lignin model compounds (ketoalcohols and ketoesters) was studied in different conditions to obtain a complete information on the erythro/threo ratios, during synthesis of guaiacylglycerol-guaiacylether. The conformation of a cetol in solution and possible transition rates were studied using 1 H and 13 CNMR analysis and it was showed that the presence of polar groups in the molecules is a preponderant factor governing the asymmetric induction

Fluoroimines from the reaction of fluoroamino acids or fluoroketo acids with the aldehyde or amine form of vitamin B6: Part III. Influence of fluorine on the formation and the reactivity of fluoroimines derived from β-fluoroaspartates or β-fluorooxaloacetate

Abstract The introduction of fluorine at the β-position in aspartate and in oxaloacetate, the typical amino acid-keto acid couple in transamination, induces large effects in their reaction with respectively pyridoxal 5′-phosphate (PLP) ( 1 ) and pyridoxamine 5′-phosphate (PMP) ( 4 ). The formation of imine intermediates through reaction of 1 with erythro or threo -β-fluoroaspartate ( 2e and 2t ) and through reaction of 4 with β-fluorooxaloacetate 5 is highly favored in comparison with that of non-fluoro compounds. The stereoisomers of the imines are unambiguously determined using a reduction reaction. The evolution of these intermediates shows that no transaminatlon is observed and that a dehydrofluorination occurs suggesting that the β-fluoro moiety in the intermediate turns into a good leaving group, changing the model reaction of transamination on α carbon through the aldimine-ketimine tautomerization to an elimination on β carbon.