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International audience; The racemization mechanism of tert-butyl-phenylphosphido-borane is investigated experimentally andtheoretically. Based on this converging approach, it is shown,first, that several phosphido-borane molecular speciescoexist at the time of the reaction and, second, that oneparticular of both initially assumed reactive routes mostsignificantly contribute to the overall racemization process.From our converging modelling and experimentalmeasurement, it comes out that the most probable species tobe here encountered is a phosphido-borane-Li(THF)2 neutralsolvate, which P-stereogenic center monomolecularinversion through a Y-shaped transition structure (ΔrG°≠: 81kJ.mol-1) brings the largest contribution to the racemizationprocess

International audience; The synthesis of P-stereogenic aminophos-phine-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.

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.

International audience; The synthesis of P,N heterobidentate phosphine / palladium complexes has been realized from P-stereogenic enantiopure ligands. Five, six or seven membered ring complexes have been fully characterized, notably by X-ray diffraction, allowing the study of the chelation to a "palladium (II) dichloride" unit. The nature of nitrogen coordination site as well as the size of the ring modify the bite-angle at the solid state.

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 β-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.

International audience; Metal-phosphinito-phosphinous acid complexes are interesting catalysts exhibiting unique reactivities. In this account, we intend to provide a clear overview of palladium-and platinum-phosphinito-phosphinous acid complexes preparation starting from secondary phosphine oxides, and their applications in catalysis. They have been mainly used to develop [2+1] cycloadditions affording methylenecyclopropane derivatives using norbornenes and various alkynes as partners. As a function of the catalyst, the reaction conditions, or the nature of the reagents, different synthetic transformations have been observed: [2+1] cycloadditions giving rise to either alkylidenecyclopropanes or vinylidenecyclopropanes, tandem [2+1]/[3+2] cycloadditions… The mechanisms of these reactions have been studied to rationalize the different reactivities observed.

International audience; Based on a previous study and in silico molecular docking experiments, we have designed and synthesized a new series of ten 5-Alkoxy-N-3-(3-PhenoxyPhenyl)-1,3,4-Oxadiazol-2(3H)-one derivatives (RmPPOX). These molecules were further evaluated as selective and potent inhibitors of mammalian digestive lipases: purified dog gastric lipase (DGL) and guinea pig pancreatic lipase related protein 2 (GPLRP2), as well as porcine (PPL) and human (HPL) pancreatic lipases contained in porcine pancreatic extracts (PPE) and human pancreatic juices (HPJ), respectively. These compounds were found to strongly discriminate classical pancreatic lipases (poorly inhibited) from gastric lipase (fully inhibited). Among them, the 5-(2-(Benzyloxy)ethoxy)-3-(3-PhenoxyPhenyl)-1,3,4-Oxadiazol-2(3H)-one (BemPPOX) was identified as the most potent inhibitor of DGL, even more active than the FDA-approved drug Orlistat. BemPPOX and Orlistat were further compared in vitro in the course of test meal digestion, and in vivo with a mesenteric lymph duct cannulated rat model to evaluate their respective impacts on fat absorption. While Orlistat inhibited both gastric and duodenal lipolysis and drastically reduced fat absorption in rats, BemPPOX showed a specific action on gastric lipolysis that slowed down the overall lipolysis process and led to a subsequent reduction of around 55% of the intestinal absorption of fatty acids compared to controls. All these data promote BemPPOX as a potent candidate to efficiently regulate the gastrointestinal lipolysis, and to investigate its link with satiety mechanisms and therefore develop new strategies to "fight against obesity".

Palladium(II) acetate in association with secondary phosphine oxides provides an efficient catalytic system for [2+1] cycloadditions starting from oxanorbornene derivatives and tertiary propargyl esters giving rise to vinylidenecyclopropanes. This reaction is specific to bidentate phosphinito-phosphinous acid ligands generated from secondary phosphine oxides. The [2+1] cycloaddition was found broad in scope with a high tolerance to various functional groups. Moreover, vinylidenecyclopropanes were straightforwardly converted into oxabicyclo[3.2.1]oct-2-ene derivatives through a palladium-catalyzed ring-expansion. Finally, the oxa bridge cleavage of oxatricyclic compounds allows the obtention of functionalized 7-membered carbocycles.

A series of [RuCl2(η(6)-p-cymene)] complexes bearing phosphinous acid (PA) ligands have been straightforwardly prepared from the dimer [RuCl2(p-cymene)]2 and secondary phosphine oxides (SPOs) and fully characterized. The steric parameter quantification of PAs, other L ligands and η(6)-p-cymene allowed a better comprehension of the coordination chemistry of these types of complexes and explained the absence of coordination in the case of bulky SPOs such as Ad2P(O)H. These complexes were tested in the C-H activation/functionalization of 2-phenylpyridine and a good activity was obtained at 80 °C for the complex exhibiting the highest steric bulk. A study on halide effects, either on the ruthenium complex or for the aryl halide partner, has also been carried out showing drastic differences. Further investigations on halide effects were performed notably by using a cationic ruthenacycle which was found to be an intermediate for the reaction. In order to rationalize the role played by the phosphinous acid, a mechanism involving a concerted metallation deprotonation favored by a phosphinito species has been proposed.

International audience; A series of [RuCl2(η 6 ‐p-cymene)]complexes bearing phosphinous acid (PA) ligands has been straightforwardly prepared from the dimer [RuCl2(p-cymene)]2 and secondary phosphine oxides (SPOs), and fully characterized. The steric parameter quantification of PAs, other L ligands and η 6 ‐p-cymene allowed a better comprehension of the coordinationchemistryof this type of complexes and explained the absence of coordination in the case of bulky SPOs such as Ad2P(O)H. These complexes were tested in theC-H activation/functionalization of 2-phenylpyridine and a good activity was obtained at 80 °C for the complex exhibiting the highest steric bulk. A study on halide effects,either on the ruthenium complex or for the aryl halide partner,has also been carried out and showed drastic differences. Further investigations on halides effects were performed notably using cationic ruthenacycle which was found to be an intermedaite of the reaction. In order to rationalize the role played by the phosphinous acid, a mechanism involving a concerted metallation deprotonation favored by a phosphinito species has been proposed.

We present recent advances in the understanding of the reduction of optically pure hydroxyalkylphosphinates and phosphine oxides, which represent key intermediates for the preparation of P-stereogenic ligands. Their reduction leads to P-chiral phosphinites and phosphines, respectively, and occurs stereospecifically with inversion of configuration using BH3·THF, which plays three roles: activating, reducing and protecting agent. The formation of by-products as hydroxyalkyl secondary phosphine–boranes has also been studied.

International audience; Palladium(II) acetate in association with secondary phosphine oxides provides an efficient catalytic system for [2+1] cycloadditions starting from oxanorbornene derivatives and tertiary propargyl esters giving rise to vinylidenecyclopropanes. This reaction is specific to bidentate phosphinito-phosphinous acid ligands generated from secondary phosphine oxides. The [2+1] cycloaddition was found broad in scope with a high tolerance to various functional groups. Moreover, vinylidenecyclopropanes were straightforwardly converted into oxabicyclo[3.2.1]oct-2-ene derivatives through a palladium-catalyzed ring-expansion. Finally, the oxa bridge cleavage of oxatricyclic compounds allows the obtention of functionalized 7-membered carbocycles.

International audience; In the present study, we propose a continuous assay for the screening of sn-2 lipases by using triacylglycerols (TAGs) from Aleurites fordii seed (tung oil) and a synthetic TAG containing the α-eleostearic acid at the sn-2 position and the oleic acid (OA) at the sn-1 and sn-3 positions [1,3-O-dioleoyl-2-O-α-eleostearoyl-sn-glycerol (sn-OEO)]. Each TAG was coated into a microplate well, and the lipase activity was measured by optical density increase at 272 nm due to transition of α-eleostearic acid from the adsorbed to the soluble state. The sn-1,3-regioselective lipases human pancreatic lipase (HPL), LIP2 lipase from Yarrowia lipolytica (YLLIP2), and a known sn-2 lipase, Candida antarctica lipase A (CALA) were used to validate this method. TLC analysis of lipolysis products showed that the lipases tested were able to hydrolyze the sn-OEO and the tung oil TAGs, but only CALA hydrolyzed the sn-2 position. The ratio of initial velocities on sn-OEO and tung oil TAGs was used to estimate the sn-2 preference of lipases. CALA was the enzyme with the highest ratio (0.22 ± 0.015), whereas HPL and YLLIP2 showed much lower ratios (0.072 ± 0.026 and 0.038 ± 0.016, respectively). This continuous sn-2 lipase assay is compatible with a high sample throughput and thus can be applied to the screening of sn-2 lipases.

The transformation of readily available pure-H-menthylphosphinates into chiral phosphinous acid-boranes permits the elaboration of bulky P-stereogenic secondary phosphine-boranes. Taking advantage of the synthetic potential of these compounds, a broad range of hindered P-chiral tertiary phosphine-boranes has been prepared with excellent enantiomeric excesses. The utility of bulky o-tolylphosphines was illustrated by the synthesis of a rare enantiopure phosphapalladacycle (S(P),S(P))-12.

Several phosphinous acid-coordinated platinum complexes were prepared and characterized. In the presence of secondary phosphine oxide (2 equiv), PtCl2(cod) was converted to a series of cis/trans platinum complexes PtCl2[R1R2POH]2 featuring phosphinous acids (PAs) as ligands (20−29). A balance between the steric and electronic effects of ligands governs their coordination mode. NMR experiments and density functional theory calculations show that the anti conformer for trans complexes is favored by intramolecular H···Cl bonding. PtCl2[R1R2POH]2 treated with NEt3 (1 equiv) gave bimetallic platinum complexes cis-[Pt2(μ-Cl)2{(R1R2PO)2H}2] characterized by 31P NMR and X-ray diffraction. An unusual monometallic platinum complex, cis-[PtCl2{(i-Bu)2PO}2H]−[HNEt3]+ (30), was isolated and characterized as a possible intermediate in the formation of dinuclear species. Silver acetate and triethylamine both reacted with PtCl2[(t-Bu)2POH]2 to yield new bulky Pt(κ2-acetato){[(t-Bu)2PO]2H} platinum complex 31. The structu...

The synthesis, structural, and conformational studies of new P-chiral triaminophosphines, which feature an indolidine and a 1,2,3,4-tetrahydroquinolidine pattern, respectively, are reported. These compounds can feature very different 3D-structures, although they both could be seen a priori as close derivatives of the previously reported 3-phenyl-1,3-diaza-2-phosphabicyclo[3.3.0]octane. The consequences for the use of such compounds and their derivatives in asymmetric metal-catalysis are discussed on the basis of preliminary results in asymmetric cobalt-catalyzed [6+2] cycloaddition.

Pd(II)-coordinated phosphinous acids catalyzed the formal enantioselective [2+1] cycloaddition of norbornene derivatives with terminal alkynes. The absolute configuration of (+)-3aa was assigned using VCD.

The enantioselective cobalt-catalyzed [6+2] cycloadditions of cycloheptatriene 1 with alkynes 2 is reported. Chiral phosphoramidites based on 3,3′-disubstituted (R)-BINOL appeared to be efficient ligands, affording the corresponding cycloadducts with good yields and up to 92 % ee. A vibrational circular dichroism study afforded the absolute configuration of new chiral (+)-(1S,6R)-7-phenyl[4.2.1]bicyclo- nonatriene 3a and (−)-(1S,6R)-7-trimethylsilyl[4.2.1]bicyclononatriene 3c.

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 PO 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.

International audience; Two series of ruthenium carbonyl complexes bearing either one secondary phosphine oxide ligand or two phosphinous acids have been synthesized and characterized. The catalytic behavior of these complexes has been then investigated for the cycloisomerization of arenynes. This study highlighted a strong relationship between ligands’ and substrates’ substructures.

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.

A new metal-catalyzed addition reaction of 1,3-diketones to ynamides, which provides access to unprecedented alkoxy- substituted enamides, is disclosed herein. A screening of cata- lytic systems showed that both a phosphapalladacycle and a cationic gold complex were capable of promoting this reac- tion rapidly and cleanly. The scope investigation revealed that variously substituted terminal ynamides and cyclic 1,3-diones were well tolerated. The use of internal ynamides led to the formation of both E and Z isomers with low to good selectivi- ties. The proposed mechanism suggests that the phosphapalla- dacycle acts as a p Lewis acid to activate the ynamide.

International audience; 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.

International audience; Whereas the reaction of norbornadiene with terminal alkynes in the presence of a phosphapalladacycle catalyst leads to the formation of hydroalkynation products, the use of phosphinous acid–phosphinito-containing palladium complexes gives rise to formal [2+1] cycloadducts. An experimental and computational approach was employed to study the mechanisms of the palladium-promoted hydroalkynation and [2+1] cycloaddition. On the one hand, experiments highlight the crucial role of acidolysis steps on the catalytic activities. On theother hand, DFT calculations demonstrate the specificity of the phosphinito–phosphinous acid ligands, that is, the non-equivalence of the two phosphorus atoms but the interchangeability of their properties. These results may have important implications for the mechanism of other palladium-catalyzed transfor- mations especially those involving phosphapalladacycles and phosphinous acid–phosphinito-containing palladium complexes

The totally diastereoselective synthesis of new P-stereogenic (o-hydroxyaryl)diazaphospholidines, in the form of their borane complexes 4a–4h, is described. The efficiency of this procedure is based both, on a one-pot and totally diastereoselective synthesis of the precursors (ortho-bromoaryloxy)diazaphosphospholidine–borane complexes 3a–3h, and on a stereoselective P–O to P–C migration rearrangement. A X-ray diffraction study of the structures of the product 4f and his precursor 3f shows unambiguously the totally stereoselectivity of the P–O to P–C rearrangement with clean retention of the phosphorus configuration.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

International audience; A synthetic phosphonate inhibitor designed for lipase inhibition but displaying a broader range of activity was covalently immobilized on a solid support to generate a function-directed tool targeting serine hydrolases. To achieve this goal, straightforward and reliable analytical techniques were developed, allowing the monitoring of the solid support's chemical functionalization, enzyme capture processes and physisorption artifacts. This grafted inhibitor was tested on pure lipases and serine proteases from various origins, and assayed for the selective capture of lipases from several complex biological extracts. The direct identification of captured enzymes by mass spectrometry brought the proof of concept on the efficiency of this supported covalent inhibitor. The features and limitations of this “enzyme-fishing” proteomic tool provide new insight on solid–liquid inhibition process.

The title compounds are prepared via a two step procedure involving a transesterification between a diol and diethyl phosphite followed by a palladium-catalyzed coupling of the so-obtained cyclic phosphite with vinyl bromide. Theoretical DFT calculations have been performed on phosphonate and phosphite anions models in order to estimate stereoelectronic effects in five-membered and six-membered ring compounds.

The crystal structures of gastric lipases in the apo form [Roussel, A., et al. (1999) J. Biol. Chem. 274, 16995-17002] or in complex with the (R(P))-undecyl butyl phosphonate [C(11)Y(4)(+)] [Roussel, A., et al. (2002) J. Biol. Chem. 277, 2266-2274] have improved our understanding of the structure-activity relationships of acid lipases. In this report, we have performed a kinetic study with dog and human gastric lipases (DGL and HGL, respectively) using several phosphonate inhibitors by varying the absolute configuration of the phosphorus atom and the chain length of the alkyl/alkoxy substituents. Using the two previously determined structures and that of a new crystal structure obtained with the other (S(P))-phosphonate enantiomer [C(11)Y(4)(-)], we constructed models of phosphonate inhibitors fitting into the active site crevices of DGL and HGL. All inhibitors with a chain length of fewer than 12 carbon atoms were found to be completely buried in the catalytic crevice, whereas longer alkyl/alkoxy chains were found to point out of the cavity. The main stereospecific determinant explaining the stronger inhibition of the S(P) enantiomers is the presence of a hydrogen bond involving the catalytic histidine as found in the DGL-C(11)Y(4)(-) complex. On the basis of these results, we have built a model of the first tetrahedral intermediate corresponding to the tristearoyl-lipase complex. The triglyceride molecule completely fills the active site crevice of DGL, in contrast with what is observed with other lipases such as pancreatic lipases which have a shallower and narrower active site. For substrate hydrolysis, the supply of water molecules to the active site might be achieved through a lateral channel identified in the protein core.

Depending on the variation of the temperature and on the nature of the substituent of alk-1-ynes 2, the enantioselectivity of the deltacyclene formation in the cobalt catalysed [2+2+2] cycloaddition of norbornadiene 1 and acetylenes 2, can be achieved with up to 98%. The best enantioselectivities observed around 14 °C are in agreement with the Isoinversion principle (IIP).

QUIPHOS-PN5, a new stable P,N ligand with a stereogenic phosphorus centre was synthesised in two steps from 8-bromoquinoline (61% yield). Its structure and its bidentate chelating ability was confirmed by the X-ray structure of a palladium(II) complex with this ligand. P(V) derivatives of QUIPHOS-PN5 were then easily obtained in excellent yields (85–100%).

International audience; A new metal-catalyzed addition reaction of 1,3-diketones to ynamides, which provides access to unprecedented alkoxy- substituted enamides, is disclosed herein. A screening of cata- lytic systems showed that both a phosphapalladacycle and a cationic gold complex were capable of promoting this reac- tion rapidly and cleanly. The scope investigation revealed that variously substituted terminal ynamides and cyclic 1,3-diones were well tolerated. The use of internal ynamides led to the formation of both E and Z isomers with low to good selectivi- ties. The proposed mechanism suggests that the phosphapalla- dacycle acts as a p Lewis acid to activate the ynamide.

The design and synthesis of a new class of chiral quinoline–phosphine ligands has been achieved. Their efficiency as asymmetric ligands in enantioselective palladium-catalyzed allylic substitution reactions and in the asymmetric copper-catalyzed addition of diethylzinc to enones was also investigated.

New developments in the enantioselective ring opening of meso-epoxides catalyzed by a chiral Lewis base have been achieved using various chloride ion silicon sources. Thus, the use of TMSCl led to enantioselectivities varying from 6 to 98% ee depending on the nature of the considered epoxide.

The synthesis of a new class of bifunctional organophosphorus catalysts for the asymmetric borane reduction of prochiral ketones has been investigated. Keys to the architecture of effective catalysts are an oxazaphospholidine structural unit and a hydroxyaryl moiety. These (o-hydroxyaryl)oxazaphospholidine oxides have been successfully applied to the catalytic (2 mol-%) asymmetric borane reduction of numerous prochiral ketones with enantiomeric excesses up to 84% ee.

Asymmetric formation of quaternary centers by allylic alkylation of β-ketoesters using the chiral palladium QUIPHOS catalyst has been achieved. The results obtained not only depend on the reaction conditions but also on the structural features of both β-ketoesters and allylating agents. Enantiomeric excesses of up to 95% have been observed.

The use of a new chiral copper catalyst involving QUIPHOS as ligand in the 1,4-addition of Et2Zn to enones is reported. The dramatic beneficial effect of addition of water or Zn(OH)2 to this system has been investigated, and led to an improvement of the enantiomeric excess from 7 to 61% ee.

The stereoselective formation of 8-substituted deltacyclanes by homo Diels–Alder (HDA) reaction using a phosphine modified nickel catalyst generated by reduction of Ni(acac) 2 with alkylaluminums is discussed. Depending on the nature of the alkene and on the nickel catalytic system, fair to excellent exo selectivity are observed. A switch in selectivity favoring the endo -cycloadduct is observed when the polar methoxycarbonyl group substituted alkene is activated with aluminum species.

The palladium(0)-catalyzed alkylation of 2,3-bis(acetoxymethyl)bicyclo[2.2.1]hepta-2,5-diene 1 with malonate-type enolates as nucleophiles is investigated. A monoalkylated product is formed first, and undergoes (depending on the nucleophile used) a second intramolecular reaction leading to spirocyclopropane-annulated bicyclo[2.2.1]heptene derivatives 5. The formation of endo spirobicyclic cyclopropanes adducts as major isomer is rationalized by assuming formation of an intermediate exo-(π-allyl)palladium complex.

Chiral bicyclic phosphanes incorporating a five- and an eight-membered ring were prepared via selective P N bond cleavage ofchiral triquinphosphoranes induced by dimethylzirconocene Cp 2 ZrMe 2 or diphenylzirconocene Cp 2 ZrPh 2 . © 2000 Elsevier ScienceS.A. All rights reserved. Keywords :Phosphoranes; Chiral phosphanes; Zirconium; Metallocene; Opening reaction 1. Introduction Zirconium derivatives were found to be useful toolsin the preparation of linear or cyclic phosphorus com-pounds [1]. We have very recently developed a largevariety of new zirconium-promoted ring-opening reac-tions [2]. This new method was applied to triquinphos-phoranes derivatives as rare examples of their opentautomers were observed [3].We have previously shown [4] that the NMR spectro-scopic data of the triquinphosphoranes are consistentwith either a time-averaged spectrum characteristic of alow-energy Berry pseudo-rotation process [5] with thehydrogen atom as the pivot between the two possiblediastereomeric trigonal pyramid structures (TBP (

Triquinphosphoranes 1 undergo alkylthiylation reactions, even in the dark, with methyl and n -butyl disulfides to give the corresponding thiaphosphoranes with high yields. Chiral triquinphosphorane 2 , by this reaction, gives rise to chiral thiatriquinphosphorane 4 . The reaction with t -BuSSBu- t preferably gave the thiophosphoramide. An increased reactivity was observed when the experiments were conducted under UV irradiation.

The synthesis of a new chiral organophosphorus derivatizing agent prepared from (S)-2-anilinomethylpyrrolidine 1 and its successful use in the determination of enantiomeric composition of various halohydrins by 31P NMR spectroscopy is described.

A mechanistic investigation into the addition of diethylzinc to aromatic aldehydes catalyzed by chiral o -hydroxyaryldiazaphosphonamides is described. A positive non-linear effect has been encountered and the X-ray structure of catalyst anti - 1 has been realized.

The influence of numerous parameters in the aromatic anionic [1,3] P–O to P–C rearrangement in the synthesis of chiral o -hydroxyaryl diazaphosphonamides has been envisaged. Various strong bases such as LDA, sec -BuLi, tert -BuLi have been conveniently used. The scope of the regioselectivity of the rearrangement has been particularly studied varying the nature of the phenoxy group implied in this reaction. A totally diastereoselective P–O to P–C migration rearrangement has been observed starting from a thiophosphonamide precursor. Moreover, starting from a phenylthio substituted phosphonamide, a totally diastereoselective P–S to P–C rearrangement of the diazaphosphonamide moiety has also been demonstrated.

Chiral triquinphosphoranes react with trifluoroacetophenone, ketopantolactone and aromatic aldehydes affording pairs of hydroxyphosphoranes diastereomers with a diastereoselectivity up to 90% depending on the nature of the electrophile. In the case of ketopantolactone, hydroxyphosphorane diastereomers are quantitatively converted to alkoxyphosphoranes with a decreasing of diastereomeric excesses. The major alkoxyphosphorane diastereomer exhibits a close SP structure determined by x-ray diffraction analysis.

Phosphonate compounds mimic the first transition state occurring during enzymatic carboxyester hydrolysis of natural substrates by forming a covalent bond with the catalytic serine. However, until now the organophosphorus compounds used in the inhibition studies more or less resembled a natural triglyceride substrate. In order to elucidate the interfacial activation and the mechanism of action of lipases, specific inhibitors need to be prepared. To achieve this goal, enantiomerically pure sn-1,2- and sn-2,3-O-didecanoylglycerol compounds were prepared – starting from a C-4 chiral synthon, 3-buten-1,2-diol – and treated with n-pentylphosphonic dichloride and p-nitrophenol to afford the corresponding diastereomeric phosphonates, which were acylglycerol analogs. Subsequent separation of each of the phosphonate diastereomers A/B or ent-A/ent-B, performed by HPLC, led to four enantiopure stereoisomers that will be investigated as inhibitors of Human Pancreatic Lipase (HPL) and Human Gastric Lipase (HGL) using the monomolecular film technique.

The synthesis of two new chiral σ2λ2-phosphenium cations 3 and 9 bearing proximal methoxy groups and their corresponding phosphine-borane adducts is reported. Phosphenium 9 has been successfully used in a chelotropic cycloaddition reaction with 2,3-dimethyl butadiene leading to the formation of a new σ4λ4-adduct.