Physical Separation of Enantiomeric Products by Compartmentalized Parallel Kinetic Resolution.

Accessing each enantiomer of a chiral molecule starting from a racemic mixture remains a daunting challenge in chemistry. Indeed, until now, only a few solutions exist to separate enantiomers of an equimolar mixture of a chiral precursor. In this study, we establish a new strategy to prepare simultaneously and physically separate both enantioenriched enantiomers of a molecule starting from a racemic substrate. This process combines two enantiomeric catalytic systems, working in parallel, and separation by an achiral membrane with selective permeability. This unprecedented system was successfully applied to the simultaneous preparation of both enantiomers of chiral 1,2-diols starting from racemic epoxides using Jacobsen's hydrolytic kinetic resolution (HKR) in parallel.

Racemization mechanism of lithium tert-butylphenylphosphido-borane: A kinetic insight.

The racemization mechanism of tert-butylphenylphosphido-borane is investigated experimentally and theoretically. Based on this converging approach, it is shown, first, that several phosphido-borane molecular species coexist at the time of the reaction and, second, that one particular of both initially assumed reactive routes most significantly contribute to the overall racemization process. From our converging modeling and experimental measurement, it comes out that the most probable species to be here encountered is a phosphido-borane-Li (THF)2 neutral solvate, whose P-stereogenic center monomolecular inversion through a Y-shaped transition structure (Δr G°≠ : 81 kJ mol-1 ) brings the largest contribution to the racemization process.

Transition metal complexes bearing atropisomeric saturated NHC ligands.

From achiral imidazolinium salts, chiral transition metal complexes containing an N-heterocyclic carbene (NHC) ligand were prepared (metal = palladium, copper, silver, gold, rhodium). Axial chirality in these complexes results from the formation of the metal-carbene bond leading to the restriction of rotation of dissymmetric N-aryl substituents about the C-N bond. When these complexes exhibited a sufficient configurational stability, a resolution by chiral high-performance liquid chromatography (HPLC) on preparative scale enabled isolation of enantiomers with excellent enantiopurities (>99% ee) and good yields. A study of the enantiomerization barriers revealed the effect of the backbone nature as well as the type of transition metal on its values. Nevertheless, the evaluation of palladium-based complexes in asymmetric intramolecular α-arylation of amides demonstrated that the ability to induce an enantioselectivity cannot be correlated to the configurational stability of the precatalysts.

The Chloroazaphosphatrane Motif for Halogen Bonding in Solution.

Chloroazaphosphatranes, the corresponding halogenophosphonium cations of the Verkade superbases, were evaluated as a new motif for halogen bonding (XB). Their modulable synthesis allowed for synthetizing chloroazaphosphatranes with various substituents on the nitrogen atoms. The binding constants determined from NMR titration experiments for Cl-, Br-, I-, AcO-, and CN- anions are comparable to those obtained with conventional iodine-based monodentate XB receptors. Remarkably, the protonated azaphosphatrane counterparts display no affinity for anions under the same conditions. The strength of the XB interaction is, to some extent, related to the basicity of the corresponding Verkade superbase. The halogen bonding abilities of this new class of halogen donor motif were also revealed by the Δδ(31P) NMR shift observed in CD2Cl2 solution in the presence of triethylphosphine oxide (TEPO). Thus, chloroazaphosphatranes constitute a new class of halogen bond donors, expanding the repertory of XB motifs mainly based on CAr-I bonds.

Enantiopure encaged Verkade's superbases: Synthesis, chiroptical properties, and use as chiral derivatizing agent.

Verkade's superbases, entrapped in the cavity of enantiopure hemicryptophane cages, have been synthesized with enantiomeric excess (ee) superior to 98%. Their absolute configuration has been determined by using electronic circular dichroism (ECD) spectroscopy. These enantiopure encaged superbases turned out to be efficient chiral derivatizing agents for chiral azides, underlining that the chirality of the cycloveratrylene (CTV) macrocycle induces different magnetic and chemical environments around the phosphazide functions.

Umpolung Reactivity of in Situ Generated Phosphido-Boranes: An Entry to P-Stereogenic Aminophosphine-Boranes.

The synthesis of P-stereogenic aminophosphine-boranes has been developed on the basis of umpolung reactivity of in situ generated alkylarylphosphido-boranes, which are normally configurationally unstable intermediates. In our case, their high configurational stability was due to the slow release of the hydroxyalkyl protecting group, together with the fast formation of the iodophosphanylborane in the presence of N-iodosuccinimide. The subsequent substitution reaction was found to proceed in moderate to good yields and in a very high stereospecifity (es) using a variety of amines as nucleophiles.

Endohedral Functionalized Cage as a Tool to Create Frustrated Lewis Pairs.

A frustrated Lewis pair (FLP) system was obtained by confinement of the Lewis base partner, a Verkade's superbase, in a molecular cavity. Whereas the model superbase lacking cavity displayed no catalytic activity in Morita-Baylis-Hillman (MBH) reactions, when associated to titanium (IV) chloride, the encaged superbase turns out to be an efficient catalyst under the same conditions. The crucial role of the endohedral functionalized cage on catalytic performance was further demonstrated by the fact that model superbases with bulky substituents were much less efficient to produce active catalysts, as well as by inhibition and substrate selection experiments. 31 P NMR spectroscopy and mass spectrometry experiments evidenced that no interaction between the Lewis acidic and basic partners occurred when the superbase was capped by a cycloveratrylene (CTV) unit, thus creating a true FLP active system.

Reduction of secondary and tertiary phosphine oxides to phosphines.

Achiral or chiral phosphines are widely used in two main domains: ligands in organometallic catalysis and organocatalysis. For this reason, the obtention of optically pure phosphine has always been challenging in the development of asymmetric catalysis. The simplest method to obtain phosphines is the reduction of phosphine oxides. The essential difficulty is the strength of the P=O bond which involves new procedures to maintain a high chemio- and stereoselectivity. The reduction can occur with retention or inversion of the stereogenic phosphorus atom depending on the nature of the reducing agent and the presence of additives. In fact, the reactivity of the phosphine oxides and the mechanism of the reduction are not always well understood. Since the first work in the 1950's, numerous studies have been realised in order to develop methodologies with different reagents or to understand the mechanism of the reaction. In the last decade, efficient stereospecific methodologies have been developed to obtain optically pure tertiary phosphines from P-stereogenic phosphine oxides. In this review, we intend to provide a comprehensive and critical overview of these methodologies.

Stereospecific Synthesis of α- and ß-Hydroxyalkyl P-Stereogenic Phosphine-Boranes and Functionalized Derivatives: Evidence of the P=O Activation in the BH3 -Mediated Reduction.

Access to hydroxy-functionalized P-chiral phosphine-boranes has become an important field in the synthesis of P-stereogenic compounds used as ligands in asymmetric catalysis. A family of optically pure α and ß-hydroxyalkyl tertiary phosphine-boranes has been prepared by using a three-step procedure from readily accessible enantiopure adamantylphosphinate, obtained by semi-preparative HPLC on multigram scale. Firstly, a two-step one-pot transformation affords the enantiopure hydroxyalkyl tertiary phosphine oxides in good yields and enantioselectivities. The third step, BH3 -mediated reduction, allows the formation of the desired phosphine-boranes with excellent stereospecifity. The mechanistic study of this reduction provides new evidence to elucidate the crucial role of the pendant hydroxy group and the subsequent activation of the P=O bond by the boron atom.

H-adamantylphosphinates as universal precursors of P-stereogenic compounds.

A new family of H-adamantylphosphinates as universal precursors of P-stereogenic ligands was obtained in one step from commercial chlorophosphines. Both enantiomers of these air- and moisture-stable intermediates can easily be separated by semipreparative chiral HPLC on a gram scale and individually undergo stereoselective transformations to afford each enantiomer of a set of P-stereogenic compounds such as secondary phosphine oxides and boron-protected monophosphines.

Enantio- and Substrate-Selective Recognition of Chiral Neurotransmitters with C3-Symmetric Switchable Receptors.

We report on the synthesis of C3-symmetric enantiopure cage molecules 1, which exhibit remarkable to exclusive enantioselective recognition properties toward chiral ammonium neurotransmitters. Strong changes in the substrate selectivity are also observed when different stereoisomers of 1 are used. Furthermore, protonation/deprotonation induces a reversible modification of the conformation of 1, which switches from an imploded to an inflated form, leading to ejection and reuptake of the guest initially encaged inside the cavity.

The Hydroxyalkyl Moiety As a Protecting Group for the Stereospecific Alkylation of Masked Secondary Phosphine-Boranes.

The synthesis of functionalized tertiary phosphine-boranes has been developed via a chemodivergent approach from readily accessible (hydroxymethyl) phosphine-boranes under mild conditions. O-Alkylation or decarbonylative P-alkylation product could be exclusively obtained. The P-alkylation reaction was found to proceed in moderate to very good yields and very high enantiospecificity (es >95%) using a variety of alkyl halides as electrophiles. The configurational stability of the sodium phosphido-borane intermediate was also investigated and allowed a deeper understanding of the reaction mechanism, furnishing secondary phosphine-boranes in moderate yield and enantiopurity.

New mesostructured organosilica with chiral sugar derived structures: nice host for gold nanoparticles stabilisation.

In this paper we describe the synthesis of functionalised mesoporous organosilicas containing a mannitol derivative in the framework. For this purpose, a bis-silylated precursor 3,4-Di-O-[3-(triethoxysilylpropyl)carbamate]-1,2:5,6-di-O-isopropylidene-D-mannitol was prepared by coupling of 1,2:5,6-di-O-isopropylidene-D-mannitol with 3-(triethoxysilylpropyl)isocyanate. The framework-functionalised materials were obtained in one step by the "direct synthesis" method which consists of a co-hydrolysis and polycondensation of a bis-silylated mannitol precursor with tetraethylorthosilicate (TEOS) in the presence of a non-ionic triblock co-polymer (P123) as structure-directing agent. Interestingly, deprotection of the 1,2,5,6 OH functional groups occurred during the material synthesis. The obtained solids were characterized by (13)C and (29)Si CP-MAS NMR, N(2) adsorption-desorption, powder X-ray diffraction, TEM and elemental analysis. We have shown that, the OH functional groups, which are released during the synthesis of the mesoporous silica, can be used for chelation of ions and stabilisation of nanoparticles. The subsequent growth of gold (0) nanoparticles in the wall has been investigated and evidenced.

The population structure of Glossina palpalis gambiensis from island and continental locations in Coastal Guinea.

BACKGROUND: We undertook a population genetics analysis of the tsetse fly Glossina palpalis gambiensis, a major vector of sleeping sickness in West Africa, using microsatellite and mitochondrial DNA markers. Our aims were to estimate effective population size and the degree of isolation between coastal sites on the mainland of Guinea and Loos Islands. The sampling locations encompassed Dubréka, the area with the highest Human African Trypanosomosis (HAT) prevalence in West Africa, mangrove and savannah sites on the mainland, and two islands, Fotoba and Kassa, within the Loos archipelago. These data are discussed with respect to the feasibility and sustainability of control strategies in those sites currently experiencing, or at risk of, sleeping sickness. PRINCIPAL FINDINGS: We found very low migration rates between sites except between those sampled around the Dubréka area that seems to contain a widely dispersed and panmictic population. In the Kassa island samples, various effective population size estimates all converged on surprisingly small values (10

Benzimidazole nitrogen-directed, regiocontrolled, lithiation of ferrocenyl- and phenyl-N-n-butylbenzimidazoles.

2-Ferrocenyl- and 2-phenyl-N-n-butylbenzimidazoles were synthesized to evaluate the influence of the benzimidazole functional group upon their directed lithiation. The regiochemistry of lithiation was studied, as well as the effect of stabilization of the lithiated species by diamine coordination using tetramethyl- ethylenediamine and (-)-sparteine. The lithiations were followed by reaction with a variety of electrophiles to give the disubstituted 2-ferrocenyl- and 2-phenyl-N-n-butylbenzimidazoles compounds. This study showed that despite a simple n-butyl function on the benzimidazole, directed lithiation was readily achieved with high regiocontrol on the ferrocenyl and phenyl groups. (-)-Sparteine failed to provide asymmetric induction in the ferrocene system, and its inefficiency is explained by intramolecular coordination of the lithiated species by the benzimidazole nitrogen, which is preferred over sparteine coordination.

Polymer-supported catalysts: enantioselective hydrogenation and hydrogen transfer reduction.

Different types of heterogenized catalysts were involved in asymmetric reactions. Hydrogen transfer reduction was performed with amino alcohols derived from poly((S)-(GMA-co-EGDMA or DVB)) and hydrogenation with BINAP grafted onto PEG or copolymerized with isocyanates as ligands. Attempts of catalysts recycling are reported.