Asymmetric Synthesis of P-Chirogenic Ferrocenyl BipheP* Diphosphine by Ephedrine-Aryne Methods and Application in Rhodium-Catalyzed Hydrogenation.

Chiral diphosphines with a biphenyl bridge and the chirality borne by the phosphorus atoms and not due to the atropoisomery of the biaryl backbone have been scarcely studied. Herein, we report the asymmetric synthesis of the (,)-2,2'-bis(ferrocenylphenylphosphino)biphenyl (BipheP*) ligand and its application in Rh-catalyzed hydrogenation. The synthesis was based on the enantioselective preparation of P-chirogenic ferrocenyl(-bromophenyl)phenylphosphine by the reaction of -phosphine-borane with 1,2-dibromobenzene and its homocoupling into BipheP*.

Enantioselective Synthesis of P-Chirogenic 1,2,3-Triazolobenzophospholes.

An enantioselective synthesis of a new class of benzophosphole-based heterocycles bearing a fused triazole ring with enantioselectivities of ≤99% is reported. The key steps of the synthesis are based on an innovative stereospecific phosphinyl N → O migration of aminophosphine-boranes into phosphinites, followed by an intramolecular cyclization. Five X-ray structures of P-chirogenic triazolobenzophospholes and a gold(I) complex were established, for assigning absolute configurations, the stereochemistry of the reactions, and the placement of the triazole substituent at the position of the P center.

P(III)-Chirogenic Phosphinite Building Blocks by Stereospecific N→O Phosphinyl Migration.

In the recent past, the chirality borne by a phosphorus center has aroused growing interest in many fields, and the development of new methodologies, notably using inexpensive reagents and simple experimental conditions, has become topical. An efficient stereoselective synthesis of P-chirogenic phosphinites useful as chiral phosphorus building blocks is herein described thanks to a new intramolecular phosphorus rearrangement based on P*(III)-phosphinyl N→O migration. This rearrangement was performed by heating at 50 °C aminophosphine-boranes, easily prepared from chiral amino alcohols, with DABCO in toluene overnight.

Al and Zn phenoxy-amidine complexes for lactide ROP catalysis.

We report the synthesis of a new generation of phenoxy-amidine ligands based on an aryloxy moiety possessing an -linked trisubstituted amidine. The reaction of the phenol-amidine proligands with aluminum and zinc alkyls gave mono- or bis-ligated complexes depending on the metal/ligand ratio used. The solid-state structure of four proligands and thirteen Zn and Al complexes has been determined by X-Ray diffraction analysis.

Bis(salicylamidine) Ligands (FAlen): A Variant of Salen with "à la Carte" Denticity.

Ethylene- and phenylene-bridged bis(salicylamidine) ligands have been readily prepared from ethylene or phenylenediamine and iminium chloride derivatives generated from ,-dialkylsalicylamides. The former, in its diprotonated form (FAlenH), reacts with AlMe to afford a zwitterionic dimethyldiphenoxyaluminate complex with the FAlen ligand monoprotonated and in a bidentate κ, fashion. A phenylene-bridged proligand behaves differently, yielding a neutral methylaluminum complex bearing a κ,,-coordinated FAlen ligand.

Novel Fat Taste Receptor Agonists Curtail Progressive Weight Gain in Obese Male Mice.

Background & Aims: The spontaneous preference for dietary lipids is principally regulated by 2 lingual fat taste receptors, CD36 and GPR120. Obese animals and most of human subjects exhibit low orosensory perception of dietary fat because of malfunctioning of these taste receptors. Our aim was to target the 2 fat taste receptors by newly synthesized high affinity fatty acid agonists to decrease fat-rich food intake and obesity.

Conception and Evaluation of Fluorescent Phosphine-Gold Complexes: From Synthesis to in vivo Investigations.

A phosphine gold(I) and phosphine-phosphonium gold(I) complexes bearing a fluorescent coumarin moiety were synthesized and characterized. Both complexes displayed interesting photophysical properties: good molar absorption coefficient, good quantum yield of fluorescence, and ability to be tracked in vitro thanks to two-photon imaging. Their in vitro and in vivo biological properties were evaluated onto cancer cell lines both human and murine and into CT26 tumor-bearing BALB/c mice.

Development of a novel highly anti-proliferative family of gold complexes: Au(i)-phosphonium-phosphines.

A family of gold(i)-phosphonium-phosphine complexes was synthesized thanks to an efficient 5-step strategy, which involves a phospha-Fries rearrangement. It enables the facile variation of the phosphonium moiety. All the complexes along with a synthetic intermediate were fully characterized (a crystal structure was obtained for two of them).

Design of P-Chirogenic Aminophosphine-Phosphinite Ligands at Both Phosphorus Centers: Origin of Enantioselectivities in Pd-Catalyzed Allylic Reactions.

We have recently patented an unprecedented stereospecific N → O phosphinyl migration process which transforms P-chirogenic aminophosphines into phosphinites. A fine design of aminophosphine phosphinite ligands (AMPP*) derived from ephedrine and bearing a P-chirogenic center either at the aminophosphine or phosphinite moiety was performed. The synthesis of AMPP* ligands with a P-chirogenic aminophosphine moiety was based on the well-established stereospecific reaction of oxazaphospholidine borane with organolithium reagents, followed by trapping with a chlorophosphine and borane decomplexation.

[60]Fullerene l-Amino Acids and Peptides: Synthesis under Phase-Transfer Catalysis Using a Phosphine-Borane Linker. Electrochemical Behavior.

A new method to link amino acid and peptide derivatives to [60]fullerene is described. It uses hydrophosphination with a secondary phosphine borane. First, the stereoselective synthesis of secondary phosphine borane amino acid derivatives was achieved by alkylation of phenylphosphine borane with γ-iodo-α-amino ester reagents under phase-transfer catalysis (PTC).

Applications and stereoselective syntheses of P-chirogenic phosphorus compounds.

Phosphorus compounds bearing chirality on the P-center are usually qualified as P-chirogenic or P-stereogenic. This chemical class concerns natural products, agrochemistry, molecular materials, biology and pharmacy, although it is certainly in coordination chemistry and in asymmetric catalysis using chiral transition metal complexes that P-chirogenic phosphorus compounds are the most used. The chiral phosphine ligands and their uses in asymmetric metal-catalyzed reactions have been widely reviewed in literature.

Designing P-Chirogenic 1,2-Diphosphinobenzenes at Both P-Centers Using P(III)-Phosphinites.

A new enantiodivergent synthesis of P-chirogenic 1,2-diphosphinobenzenes (DP*B) bearing the chirality on one or both phosphorus centers is reported using aryne chemistry. The principle is based on successive reactions of 1,2-dibromobenzene with sec-phosphide boranes, then DABCO to remove the borane, and finally with chlorophosphines or P(III)-chirogenic phosphinites. The efficiency of this synthesis was demonstrated by the stereoselective preparation of (S,S)-1,2-bis(o-anisylphenylphosphino)benzene.

Efficient synthesis of (P-chirogenic) o-boronated phosphines from sec-phosphine boranes.

An efficient synthesis of boronated phosphines with an o-phenylene-bridge prepared from sec-phosphine boranes and using benzyne chemistry is reported. Successive reactions of sec-phosphine boranes with n-BuLi and 1,2-dibromobenzene, and then with boron reagents, afford the o-boronatophenylphosphine derivatives in 71% yields. The use of P-chirogenic sec-phosphine boranes leads to the free boronated phosphines with retention of configuration at the P-center after decomplexation.

P-chirogenic organocatalysts: application to the aza-Morita-Baylis-Hillman (aza-MBH) reaction of ketimines.

The P-chirogenic organocatalysts were found to promote the enantioselective aza-Morita-Baylis-Hillman reaction of ketimines derived from acyclic α-keto esters. In the P-chirogenic organocatalyzed aza-MBH reactions, α,α-disubstituted α-amino acid derivatives were obtained in high yields with high enantioselectivities (up to 97% ee).

o-(Hydroxyalkyl)phenyl P-chirogenic phosphines as functional chiral Lewis bases.

The stereoselective synthesis of P-chirogenic phosphines bearing an o-hydroxyalkyl chelating arm is described. The synthesis is based either on the hydroxyalkylation of P-chirogenic o-bromophenylphosphines (borane) or on their carbonatation and then reduction. The hydroxyalkylation with benzaldehyde or pivalaldehyde affords a mixture of epimers which are isolated by chromatography and characterized by their X-ray structures.

Stereoselective synthesis of unsaturated and functionalized L-NHBoc amino acids, using Wittig reaction under mild phase-transfer conditions.

The stereoselective synthesis of a new amino acid phosphonium salt was described by quaternization of melting triphenylphosphine with the γ-iodo NHBoc-amino ester, derived from L-aspartic acid. The deprotection of the carboxylic acid function to afford the phosphonium salt with a free carboxylic acid group was achieved by a palladium-catalyzed desallylation reaction. This phosphonium salt was used in the Wittig reaction with aromatic or aliphatic aldehydes and trifluoroacetophenone, under solid-liquid phase-transfer conditions in chlorobenzene and in the presence of K(3)PO(4) as weak base, to afford the corresponding unsaturated amino acids without racemization.

Stereoselective synthesis of P-chirogenic dibenzophosphole-boranes via aryne intermediates.

A new aryne-mediated tandem cross-coupling/P-cyclization sequence starting from tertiary phosphine-boranes and 1,2-dibromobenzenes is reported. P-chirogenic dibenzophospholes become accessible in a regio-, chemo-, and diastereoselective way.

Stereoselective synthesis of o-bromo (or iodo)aryl P-chirogenic phosphines based on aryne chemistry.

The efficient synthesis of chiral or achiral tertiary phosphines bearing an o-bromo (or iodo)aryl substituent is described. The key step of this synthesis is based on the reaction of a secondary phosphine borane with the 1,2-dibromo (or diiodo)arene, owing to the formation in situ of an aryne species in the presence of n-butyllithium. When P-chirogenic secondary phosphine boranes were used, the corresponding o-halogeno-arylphosphine boranes were obtained without racemization in moderate to good yields and with ee up to 99%.

Efficient synthesis of quaternary and P-stereogenic phosphonium triflates.

An efficient and general method for the preparation of achiral and chiral phosphonium salts is reported. This synthesis is based on the quaternization of phosphines and their derivatives with arynes generated in situ from 2-(trimethylsilyl)aryl triflates. This methodology is successfully applied to the synthesis of new valuable P-stereogenic phosphonium triflates.

Organic carbonates as alternative solvents for asymmetric hydrogenation.

Organic carbonates like propylene carbonate (PC) or butylene carbonate (BC) belong to the class of aprotic, highly dipolar solvents (AHD). Interestingly, their potential as solvents for asymmetric catalysis has been overlooked for a long time. The aim of this work is to evaluate organic carbonates and other organic solvents like THF, CH(2)Cl(2), and acetonitrile as well as members of the AHD-family (DMF, DMSO, etc.

Ferrocenyl glycopeptides as electrochemical probes to detect autoantibodies in multiple sclerosis patients' sera.

Glycopeptide analogues of CSF114(Glc), modified at N-terminus with new ferrocenyl carboxylic acid and a new ferrocenyl-thiphosphino amino acid, were used to implement a new electrochemical biosensor for autoantibody detection in multiple sclerosis. The ferrocenyl moiety of these "electrochemical probes" did not affect autoantibody recognition both in SP-ELISA and in inhibition experiments. By electrochemical monitoring the interactions of the modified peptides Fc-CSF114(Glc) and 4-FcPhP(S)Abu-CSF114(Glc) with the autoantibodies, we demonstrated that autoantibodies could be detected with a sensitivity comparable to ELISA method.

Enantiopure fluorous bis(oxazolines): synthesis and applications in catalytic asymmetric reactions.

Various enantiopure fluorous bis(oxazolines) with fluorine content between 52.7 and 58.7% have been synthesized by a simple reaction sequence that involved the introduction of two fluorinated ponytails by alkylation of the corresponding nonfluorous bis(oxazolines).