A biocatalytic route to P-chirogenic compounds by lipase-catalyzed desymmetrization of a prochiral phosphine-borane

[reaction: see text] Available methods for synthesis of P-chirogenic compounds are limited. We set out to find biocatalytical means to introduce asymmetry in a phosphine-borane. After screening different lipases, Candida antarctica lipase B was found to give excellent results in the desymmetrization of prochiral phosphine-boranes. Both enantiomers can be obtained in up to >98% optical purity via acetylation or hydrolysis in processes that allow recycling of the substrates.     

Synthesis and X-Ray Crystal Structure of an Optically Pure Tripodal C3-Symmetric Tritertiary Phosphine Bearing Chirality on Phosphorus

The preparation of the optically pure tritertiary phosphine (RRR)-MeSi(CH2P(t-Bu)Ph)3 (2) is reported. The route followed involves deprotonation of optically pure (R)-P(BH3)Me(t-Bu)PH (2) the reaction of the resulting carbanion with MeSiCl3, followed by removal with morpholine of the BH3-protecting groups from the triertiary phosphine-borane 3 . The latter's X-ray crystal structure and that of [Rh(NBD)((RRR)- 1 ]TOf)( 4 ), are also rported. Furthermore, it is shown that the separation of the racemic phosphine-borane 2 can be conveniently carried out using medium-pressure liquid chromatgrapy with cellulose-riacetate as a chiral stationary phase.     

Chemical functionality of poly(methylenephosphine): phosphine-borane adducts and methylphosphonium ionomers

The chemical functionality of poly(methylenephosphine) n-Bu[MesP-CPh(2)](n)H () is examined in reactions with two isoelectronic species, namely BH(3) and CH(3)(+). The potential reactivity of polymer is modelled by examining the reactivity of molecular phosphines bearing similar substituents as the polymer. In particular, the phosphine-borane adducts Mes(Me)P(BH(3))-CPh(2)H () and Mes(Me)P(BH(3))-CPh(2)SiMe(2)H () are prepared from the reaction of BH(3).SMe(2) with Mes(Me)P-CPh(2)H () or Mes(Me)P-CPh(2)SiMe(2)H (), respectively. Treating with MeOTf affords the methylated model compound, [Mes(Me)(2)P-CPh(2)H]OTf (). X-Ray crystal structures are reported for each model compound. The reaction of n-Bu[MesP-CPh(2)](n)H (M(n) = 3.89 x 10(4), PDI = 1.34) with BH(3).SMe(2) affords the phosphine-borane polymer n-Bu[MesP(BH(3))-CPh(2)](n)H () (M(n) = 4.13 x 10(4), PDI = 1.26). In contrast, methylation of phosphine polymer gives n-Bu[MesP-CPh(2)](x)-/-[MesP(Me)-CPh(2)](y)H.(OTf)(y) () where approximately 50% of the phosphine moieties are methylated (from (31)P NMR).     

A highly efficient general synthesis of phosphine-borane complexes

A general synthesis of phosphine-borane complexes proceeding in high yield in a safe, green process from borane generated in situ from sodium borohydride is described. The procedure also allows simultaneous carbonyl reduction and phosphine-borane formation on air-sensitive bulky phosphine derivatives.     

Intermediates in the Rh-catalysed dehydrocoupling of phosphine-borane

Active species, product distributions and a suggested catalytic cycle are reported for the dehydrocoupling of the phosphine-borane H(3)B·P(t)Bu(2)H to give HP(t)Bu(2)BH(2)P(t)Bu(2)BH(3) using the [Rh(COD)(2)][BAr(F)(4)] pre-catalyst.     

Synthesis and dehydrocoupling reactivity of iron and ruthenium phosphine-borane complexes

The Fe and Ru phosphine-borane complexes CpM(CO)2PPh2 x BH3 (1, M = Fe, 4, M = Ru) were synthesized utilizing the reaction of the phosphine-borane anion Li[PPh2 x BH3] with the iodo complexes CpM(CO)2I. The Fe complex 1 reacted with PMe3 to yield CpFe(CO)(PMe3)(PPh2 x BH3) (2) and CpFe(PMe3)2(PPh2 x BH3) (3) whereas the Ru species 4 gave only CpRu(CO)(PMe3)(PPh2 x BH3) (5). The complexes 1-5 were characterized by 1H, 11B, 13C and 31P NMR spectroscopy, MS, IR and X-ray crystallography for 1 to 4, and EA for 1, 2 and 4. The reactivity of 1 and 4 towards PPh2H x BH3 was explored. Although no stoichiometric reactions were detected under mild conditions, both 1 and 4 were found to function as dehydrocoupling catalysts to afford Ph2PH x BH2 x PPh2 x BH3 in the melt at elevated temperature (120 degrees C). The carbonyl Fe2(CO)9 also functioned as a dehydrocoupling catalyst under similar conditions. Complex 1 and Fe2(CO)9 represent the first reported active Fe complexes for the catalytic dehydrocoupling of phosphine-borane adducts.     

P-chiral o-phosphinophenol as a P/O hybrid ligand: preparation and use in Cu-catalyzed asymmetric conjugate addition of diethylzinc to acyclic enones

[reaction: see text] (S)-2-(tert-Butylmethylphosphino)phenol and its methyl ether were synthesized from tert-butyldichlorophosphine via optically active phosphine-boranes as the intermediates. The former compound was used as a P/O hybrid ligand in the Cu-catalyzed asymmetric conjugate addition of diethylzinc to acyclic enones to achieve high enantioselectivity of up to 96%.     

Structural importance of secondary interactions in molecules: origin of unconventional conformations of phosphine-borane adducts

The series of phosphine-borane adducts, Ph2(H3C--C[triple chemical bond]C)P--B(C6F5)3 (8 c), Ph(H3C--C[triple chemical bond]C)2P--B(C6F5)3 (8 b) and (H3C--C[triple chemical bond]C)3P--B(C6F5)3 (8 a), was prepared. The X-ray crystal structure analyses revealed close to eclipsed conformations for all members of this series with average dihedral angles theta(C-P-B-C) of 8.1 degrees (8 c), 12.3 degrees (8 b) and 20.3 degrees (8 a). Quantum chemical analysis of these compounds revealed the importance of a subtle interplay between competing attractive and repulsive secondary interactions, causing the surprising eclipsed conformational preference for systems of this degree of complexity. Some cyclic phosphine-borane adducts were studied for comparison.     

An Efficient Strategy to Orthogonally Protected (R)- and (S)-alpha-Methyl(alkyl)serine-Containing Peptides via a Novel Azlactone/Oxazoline Interconversion Reaction

A novel strategy for the synthesis of (R)- and (S)-alpha-methyl(alkyl)serine-containing peptides is presented. Using (S)-phenylalanine cyclohexylamide 6 as chiral auxiliary, the optically pure azlactones (R)- and (S)-2 were synthesized via a novel azlactone/oxazoline interconversion reaction (Figures 3 and 6). These azlactones constitute fully protected and activated synthetic equivalents of (R)- and (S)-alpha-methylserine and can be directly incorporated into peptides without further protective group manipulations. Like other alpha,alpha-dialkylated glycines, optically pure alpha-alkylserines can be used to stabilize beta-turn and alpha-helical conformations in short peptides.     

Platinum(II) complexes incorporating racemic and optically active 1-alkyl-3-phospholenes and 1-propyl-phospholane P-ligands: Synthesis, stereostructure, NMR properties and catalytic activity

Racemic and optically active 1-propyl- and 1-butyl-3-methyl-3-phospholene oxides, as well as 1-propyl-3-methylphospholane oxides were converted after deoxygenation to the corresponding phosphine-borane and phopshine-platinum complexes. Stereostructure of the novel platinum complexes with a propyl group on the phosphorus atom was evaluated by quantum chemical calculations. The complexes displayed characteristic properties regarding their NMR spectra and showed unusual regioselectivity as catalysts in the hydroformylation of styrene derivatives. Ee-s up to 21% were obtained in the presence of optically active Pt-complex precursors.     

Rhodium-catalyzed dehydrocoupling of fluorinated phosphine-borane adducts: synthesis, characterization, and properties of cyclic and polymeric phosphinoboranes with electron-withdrawing substituents at phosphorus

The dehydrocoupling of the fluorinated secondary phosphine-borane adduct R2PH.BH3 (R = p-CF3C6H4) at 60 degrees C is catalyzed by the rhodium complex [{Rh(mu-Cl)(1,5-cod)}2] to give the four-membered chain R2PH-BH2-R2P-BH3. A mixture of the cyclic trimer [R2P-BH2]3 and tetramer [R2P-BH2]4 was obtained from the same reaction at a more elevated temperature of 100 degrees C. The analogous rhodium-catalyzed dehydrocoupling of the primary phosphine-borane adduct RPH2.BH3 at 60 degrees C gave the high molecular weight polyphosphinoborane polymer [RPH-BH2]n (Mw = 56,170, PDI = 1.67). The molecular weight was investigated by gel permeation chromatography and the compound characterized by multinuclear NMR spectroscopy. Interestingly, the electron-withdrawing fluorinated aryl substituents have an important influence on the reactivity as the dehydrocoupling process occurred efficiently at the mildest temperatures observed for phosphine-borane adducts to date. Thin films of polymeric [RPH-BH2]n (R = p-CF3C6H4) have also been shown to function as effective negative-tone resists towards electron beam (e-beam) lithography (EBL). The resultant patterned bars were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM) and time-of-flight secondary ion mass spectrometry (TOF-SIMS).     

Resolution and stereochemistry of tert-butylphenylphosphinous acid-borane

A combined use of ephedrine and cinchonine as resolving agents enabled facile resolution of racemic tert-butylphenylphosphinous acid-borane (1) into the two enantiomers in ca. 31-32% yield each. The resolved 1 served as a model substrate to study stereoselective synthetic transformations of phosphinous acid-boranes yielding optically active phosphinite-borane, boranatophosphinous-sulfonic anhydride, secondary phosphine-borane, tertiary phosphine-borane, secondary phosphine oxide, and phosphinic halides. By the judicious choice of the reaction paths, either enantiomer of tert-butylphenylphosphine-borane and of tert-butylmethylphenylphosphine-borane could be stereoselectively obtained from a single enantiomer of 1.     

Unusual concerted Lewis acid-Lewis base mechanism for hydrogen activation by a phosphine-borane compound

Density functional theory calculations have been carried out to investigate the possible reaction mechanisms for the reversible dihydrogen activation catalyzed by a phosphine-borane compound, (C6H2Me3)2P(C6F4)B(C6F5)2 (Welch, G. C.; Juan, R. R. S; Masuda, J. D.; Stephan, D. W. Science. 2006, 314, 1124-1126). The present calculations show that an unusual concerted Lewis acid-Lewis base mechanism is more favorable than the proton transfer or hydride transfer mechanisms suggested previously. In the concerted Lewis acid-Lewis base mechanism, the H-H heterolytic cleavage is achieved through the simultaneous electron transfer from the lone-pair orbital of the Lewis base P center to the sigma* orbital of H2 and from the sigma orbital of H2 to the empty orbital of the Lewis acid B center. The solvent is found to dramatically change the potential energy surface. The proposed mechanism can account well for the bimolecular H-D exchange process observed in deuteration experiments and the experimental fact that the H2 activation is reversible at mild conditions.     

Asymmetric synthesis of (s)-methyl-3-hydroxyalkanoates from ketene and 2,2-dichloroaldehydes via 4-(1,1-dichloroalkyl)-2-oxetanones

Using the quinidine catalysed cycloaddition reaction of ketene and 2,2-dichloroaldehydes, the preparation of several optically pure (S)-methyl-3-hydroxyalkanoates is reported.     

Nucleophilic aromatic substitution reactions of fluorobenzenechromium complexes with P-chiral secondary phosphine-boranes: synthesis of optically pure P-chiral (dialkyl)arylphosphine-boranes

Optically pure P-chiral (dialkyl)arylphosphine-boranes having high structural diversity were prepared by two- or three-component coupling of fluorobenzenechromium complexes, P-chiral secondary phosphine-boranes, and other nucleophiles. The stereochemical integrity at the P-stereogenic center was completely retained during the S_NAr process when the reaction was carried out in THF at low temperature.     

Chemistry of phosphine-borane adducts at platinum centers: dehydrocoupling reactivity of Pt(II) dihydrides with P-H bonds

The reaction of the Pt(II) dihydride complex cis-[PtH2(dcype)](dcype = 1,2-bis(dicyclohexylphosphino)ethane) with the primary or secondary phosphine-borane adducts PhRPH x BH3(R = H, Ph) was found to exclusively afford the mono-substituted complexes cis-[PtH(PPhR x BH3)(dcype)](1: R = H; 2: R = Ph)via a dehydrocoupling reaction between Pt-H and P-H bonds. Similar reactivity was observed between the uncoordinated phosphines PhRPH (R = H, Ph) and cis-[PtH2(dcype)], which gave cis-[PtH(PPhR)(dcype)](4: R = H; 5: R = Ph). The complexes were characterized by 1H, 11B, 13C and 31P NMR spectroscopy, IR, MS and, in the case of 2, X-ray crystallography that confirmed the cis geometries. The di-substituted complex cis-[Pt(PhPH x BH3)2(dcype)](3) was prepared from the reaction of cis-[PtCl2(dcype)] with two equivalents of Li[PPhH x BH3]. This suggested that steric reasons alone cannot be used to explain the lack of reactivity with respect to a second dehydrocoupling reaction involving the remaining Pt-H bond in complexes 1, 2, 4 and 5.     

Synthesis of chiral nonracemic 1-(2-pyridinyl)ethylamines: stereospecific introduction of amino function onto the 2-pyridinylmethyl carbon center

Stereospecific substitutions of optically pure 1-(pyridinyl)ethyl methanesulfonates with various amines are described. The reaction of (R)- or (S)-1-(2-pyridinyl)ethyl methanesulfonate with primary amines, including amino acid esters, gives N-substituted (S)- or (R)-1-(2-pyridinyl)ethylamines (4) with inversion of the configuration. Secondary cyclic amines are also reacted with (R)-2 to give the corresponding substituted amines (5) in excellent yields. Optically pure and meso triamine ligands having two pyridine rings, (S,S)-4f and meso-4f, (S,S)-9e, (S,R)-9e, and (S,S)-9f, have been prepared in stereochemically pure form by this method. Not only the substitution reaction of optically active 2 but also that of 1-(4-pyridinyl)ethyl and 1-(3-pyridinyl)ethyl methanesulfonates 11 and 14 take place stereospecifcally with inversion of the chiral center.     

手性4-膦酸二酯基-3-卤-2(5H)-呋喃酮的合成与结构

手性呋喃酮1a-1b与亚磷酸三酯2a-2b通过串联的不对称Michael加成/分子内Michalis-Arbazov重排反应,得到了含磷官能团的新手性化合物,5-(S)-(l-孟氧基)-4-膦酸二酯基-3-卤素-2(5H)-呋喃酮4a-4d。该反应具有条件温和,产率高(86%-95%),光学纯度单一(d.e.≥98%)的特点。通过元素分析,IR,UV,^1HNMR,^1^3CNMR,MS,[α]~D^2^0波谱分析数据以及X射线四圆衍射数据确定了它们的化学结构和绝对构型。     

Asymmetric oxidation and determination of the configurations of an optically pure sulfoxide and an I-menthoxysulfonium salt of 1,9-bis(methylthio)dibenzothiophene by x-ray crystallographic analysis

1,9-Bis(methylthio)dibenzothiophene (1a) was treated with one equivalent of bromine and pyridine in the presence of l-menthol and then with aqueous sodium hydroxide to give optically active 1-(methylsulfinyl)-9-(methylthio)dibenzothiophene (2a) enriched by the S isomer (ee: 57%). The configuration of optically pure sulfoxide (2a) was determined by X-ray crystallographic analysis to be the S configuration at the sulfinyl sulfur atom. On the other hand, 1-(methyl-l-menthoxysulfonio)-9-(methylthio)dibenzothiophene tetrafluoroborate (4a) was isolated as an intermediate of this asymmetric oxidation in an optically pure form, as yellow crystals. The absolute configuration of this sulfonium salt (4a) was verified by X-ray crystallographic analysis as the R configuration. Optically pure sulfonium salt (4a) also gave partially optically active sulfoxide (2a) with net inversion on its hydrolysis. It was suggested that the hydrolysis reaction of the sulfonium salt (4a) accordingly proceeds, not only via a sulfurane having a simple S_N2 type of geometry but also by a front side attack ofhydroxide anion, with respect to the l-menthoxy group, on sulfur, and the sequential elimination of the l-menthoxy group from the tetracoordinated intermediate. © 1996 John Wiley & Sons, Inc.     

Volatile organogold compounds [AuR(CNR1)]: Their potential for chemical vapour deposition of gold

The preparation and characterization of a series of novel volatile organogold compounds of the type [AuR(CNR¹)], where R = methyl, phenyl, vinyl, 1-propynyl and 3,3-dimethyl-butynyl, and R¹ = methyl, ethyl, i-propyl, t-butyl, phenyl and cyclohexyl, are described. These compounds show sharply differing thermal stabilities. As a result of their volatility, the more stable members of the series have potential as chemical vapour deposition agents, selectively yielding essentially pure gold films under conditions of high vacuum and moderate temperature. This principle is demonstrated for these and other known volatile organogold compounds.