Second generation levoglucosenone-derived chiral auxiliaries. Scope and application in asymmetric Diels-Alder reactions

Chiral alcohols were designed and easily prepared from levoglucosenone, a biomass-derived valuable synthon. These alcohols were tested as chiral auxiliaries in asymmetric Diels-Alder reactions between the corresponding acrylates with acyclic and cyclic dienes. The regio, stereo, and facial selectivity varied from very good to excellent, depending upon the benzylic substitution of the auxiliary and the diene employed. As a consequence, after removal of the auxiliary, the resulting carboxylic acid derivatives were obtained in 72-99% ee.     

The investigation of structural and thermosensitive properties of new phosphazene derivatives bearing glycol and amino acid

In this study, hexachlorocyclotriphosphazene, N(3)P(3)Cl(6) (cylotriphosphazene), was reacted with hydrophilic and hydrophobic groups to synthesize amphiphilic phosphazene derivatives (4-12). Cylotriphosphazene was reacted triethylene glycol monomethyl ether (TEGME), dipropylene glycol monomethyl ether (DPGME), diethylene glycol monobutyl ether (DEGBE), (1 : 3 mole proportion) in the presence of sodium hydride and using tetrahydrofuran (THF) as solvent at -60 °C. Three isomers (nongeminal cis-2,4,6 (1a-3a); nongeminal trans-2,4,6 (1b-3b); geminal 2,2,4 (1c-3c)) were isolated from the reaction of hexachlorocyclotriphosphazatriene (trimer) (1) with TEGME, DPGME and DEGBE. The substitution reactions of cis-tris isomers (1a-3a) with 4-amino butyric acid, 5-amino valeric acid and 6-amino hexanoic acid were separately done to provide amphiphilic phosphazenes (4-12). All compounds were characterized by using elemental analysis, (31)P NMR and mass spectroscopy. Thermosensitive properties of compounds were studied. The compounds (4-12) were soluble in both water and organic media that shows they are amphiphilic molecules. Concentration-dependent LCST (Lower Critical Solution Temperature) behaviours of new compounds (4-12) were measured in water. Compounds 7, 9, 11 and 12 exhibited a reversible and thermosensitive phase transition in aqueous medium, from soluble to insoluble states.     

Synthesis and spectroscopy of N3P3X5OCH=CH2 (X = Cl, F, OCH3, OCH2CF3, N(CH3)2) and N3P3X4(OCH=CH2)2 (X = Cl, N(CH3)2). Correlations of ultraviolet photoelectron spectroscopy and nuclear magnetic resonance data to electronic and geometrical structure

The syntheses of the vinyloxycyclotriphosphazene derivatives N3P3X5OCH=CH2 (X = OMe, OCH2CF3) and the N3P3(NMe2)4(OCH=CH2)2 isomeric mixture along with improved preparations of N3P3X5OCH=CH2 (X = F, NMe2) are reported. The interactions between the vinyloxy function and the cyclophosphazene in these and the previously reported N3P3Cl5 (OCH=CH2) and N3P3F6-n(OCH=CH2)n (n = 1-4) have been examined by ultraviolet photoelectron spectroscopy (UPS) and NMR spectroscopy. The UPS data for the chloro and fluoro derivatives show a strong electron-withdrawing effect of the phosphazene on the olefin that is mediated with decreasing halogen substitution. The 1H and 13C NMR data for N3P3X5OCH=CH2 (X = F, Cl, OMe, OCH2CF3, NMe2) show significant changes as a function of the phosphazene substituent. There is a linear correlation between the beta-carbon chemical shift on the vinyloxy unit and the phosphorus chemical shift at the vinyloxyphosphorus centers. The chemical shifts of the different phosphorus centers on each ring are also related in a linear fashion. These relationships may be understood in terms of the relative electron donor-acceptor abilities of the substituents on the phosphazene ring. The 1H NMR spectra of the N3P3(NMe2)4(OCH-CH2)2 isomeric mixture allow for assignment of the relative amounts of cis and trans isomers. A model for the observed cis preference in the formation of N3P3Cl4(OCH=CH)2 is presented.     

Neutral and zwitterionic low-coordinate titanium complexes bearing the terminal phosphinidene functionality. Structural, spectroscopic, theoretical, and catalytic studies addressing the Ti-P multiple bond

Alpha-hydrogen abstraction and alpha-hydrogen migration reactions yield novel titanium(IV) complexes bearing terminal phosphinidene ligands. Via an alpha-H migration reaction, the phosphinidene ((tBu)nacnac)Ti=P[Trip](CH(2)(tBu) ((tBu)nacnac(-) = [Ar]NC((t)Bu)CHC((t)Bu)N[Ar], Ar = 2,6-(CHMe2)(2C6H3, Trip = 2,4,6-(i)Pr3C6H2) was prepared by the addition of the primary phosphide LiPH[Trip] to the nucleophilic alkylidene triflato complex ((tBu)nacnac)Ti=CH(t)Bu(OTf), while alpha-H abstraction was promoted by the addition of LiPH[Trip] to the dimethyl triflato precursor ((tBu)nacnac)Ti(CH)(2)(OTf) to afford ((tBu)nacnac)Ti=P[Trip](CH3). Treatment of ((tBu)nacnac)Ti=P[Trip](CH3) with B(C6F5)(3) induces methide abstraction concurrent with formation of the first titanium(IV) phosphinidene zwitterion complex ((tBu)nacnac)Ti=P[Trip]{CH3B(C6F5)(3)}. Complex ((tBu)nacnac)Ti=P[Trip]{CH3B(C6F5)(3)} [2 + 2] cycloadds readily PhCCPh to afford the phosphametallacyclobutene [((tBu)nacnac)Ti(P[Trip]PhCCPh)][CH3B(C6F5)(3)]. These titanium(IV) phosphinidene complexes possess the shortest Ti=P bonds reported, have linear phosphinidene groups, and reveal significantly upfielded solution 31P NMR spectroscopic resonances for the phosphinidene phosphorus. Solid state 31P NMR spectroscopic data also corroborate with all three complexes possessing considerably shielded chemical shifts for the linear and terminal phosphinidene functionality. In addition, high-level DFT studies on the phosphinidenes suggest the terminal phosphinidene linkage to be stabilized via a pseudo Ti[triple bond]P bond. Linearity about the Ti-P-C(ipso) linkage is highly dependent on the sterically encumbering substituents protecting the phosphinidene. Complex ((tBu)nacnac)Ti=P[Trip]{CH3B(C6F5))(3)} can catalyze the hydrophosphination of PhCCPh with H(2)PPh to produce the secondary vinylphosphine HP[Ph]PhC=CHPh. In addition, we demonstrate that this zwitterion is a powerful phospha-Staudinger reagent and can therefore act as a carboamination precatalyst of diphenylacetylene with aldimines.     

State in solution, structure, and regioselectivity of reactions of the lithium 1-(2-methoxyphenyl)-3,3-diphenylpropyne derivative

According to the spectrophotometric data, the lithium 1-(2-methoxyphenyl)-3,3-diphenylpropyne derivative in diethyl ether exists as contact ion pairs, while in THF, according to the spectrophotometric and¹³C NMR data, solvent-separated ion pairs are predominantly formed. According to the¹³C NMR data, the carbanion in the solventseparated ion pairs has a structure close to the propargylic type. The regioselectivity of reactions of the lithium derivative with ethyl halides in diethyl ether, THF, and hexamethyphosphoramide, with benzyl chloride in the first two solvents, and with methanol in THF were studied. The protonation with methanol proceeds exclusively at the allenylic center (C-1) while the ethylation and especially benzylation proceed predominantly at the propargylic center (C-3). The selectivity of ethylation of the propargylic center of both solvent-separated ion pairs in THF and contact ion pairs in diethyl ether increases as the hardness of the ethylating agent increases, and in the case of the same ethyl halide, the selectivity increases from the solvent-separated ion pairs to the contact ion pairs. The spectral data obtained and the data on changes in the regioselectivity do not allow one to believe that the contact ion pairs of the lithium derivative in ether exhibit the intramolecular coordination of the lithium cation to the methoxy group, which might lead to the allenylic structure of contact ion pairs of this derivative. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2043–2051, November, 1997.     

DFTMP, an NMR reagent for assessing the near-neutral pH of biological samples

A new NMR chemical shift standard and pH indicator, difluorotrimethylsilanylphosphonic acid (DFTMP), is described, and the utility of this reagent is demonstrated for in situ determination of pH in complex biofluids. The pH dependence of this reagent allows accurate in situ determination of aqueous solution pH to within an RMSE of 0.02 pH units over a pH range of 5 to 8. Advantages of this reagent over previously described pH-sensitive components include (1) lack of metal binding affinity, (2) minimal disturbance of endogenous spectral regions, and (3) the potential to function as a multinuclear pH indicator and chemical shift reference point for 19F, 1H, and 31P nuclei. This reagent will be generally useful for NMR experiments on biological systems where the pH needs to be accurately measured at the moment of data acquisition.     

1,3-Dimethyl-2-(3-nitro-1,2,4-triazol-1-yl)-2-pyrrolidin-1-yl-1,3,2-diazaphospholidinium hexafluorophosphate (MNTP): a powerful condensing reagent for phosphate and phosphonate esters

A novel phosphonium-type condensing reagent, 1,3-dimethyl-2-(3-nitro-1,2,4-triazol-1-yl)-2-pyrrolidin-1-yl-1,3,2-diazaphospholidinium hexafluorophosphate (MNTP), was designed and synthesized. A ³¹P NMR study on the condensation reactions of phosphate, alkylphosphonate, boranophosphate, and H-phosphonate derivatives with an alcohol in the presence of MNTP demonstrated the versatility and the enhanced activity of the new condensing reagent, compared to the previously reported phosphonium-type condensing reagents. The mechanism of the condensation reactions mediated by MNTP is discussed on the basis of the ³¹P NMR studies and theoretical calculations.     

Selective adduct formation by furan chemical ionization reagent in gas chromatography ion trap mass spectrometry

The analytical potential of furan as a chemical ionization (CI) reagent was evaluated for selectivity with nine monosubstituted naphthalene compounds. The ion-molecule reactions of furan and tetrahydrofuran (THF) were compared with those of methane, methanol and acetonitrile (prominently producing [M + H](+) ion base peaks) with naphthalene compounds in chemical ionization mass spectrometry (CI-MS). Reactions with furan predominantly show M(+) and [M + 39](+) ions. Based on this phenomenon, investigations were carried out for some of the molecular factors such as proton affinity, substituent effects and the preferred site of [C(3)H(3)](+) ion attachment that influence reactivity in furan CI. High selectivity with different substituents is observed in the formation of [M + 39](+) adduct ion, suggesting its usefulness as selective ionization reagent liquid. The selectivity and sensitivity are illustrated in the analysis of mixture of amino acids. Furthermore, the structure determination and reaction mechanism study is characterized by collision-activated dissociation experiments in CI-MS/MS and CI-MS/MS/MS.     

Phosphorus-nitrogen compounds. Part 13. Syntheses, crystal structures, spectroscopic, stereogenic, and anisochronic properties of novel spiro-ansa-spiro-, spiro-bino-spiro-, and spiro-crypta phosphazene derivatives

The condensation reactions of N2Ox (x = 2, 3) donor-type aminopodand (4) and dibenzo-diaza-crown ethers (5, 6, and 9) with hexachlorocyclotriphosphazatriene, N3P3Cl6, produce two kinds of partially substituted novel phosphazene derivatives, namely, spiro-bino-spiro- (19) and spiro-crypta (21, 22, and 25) phosphazenes. The partially substituted spiro-ansa-spiro-phosphazene (11) reacted with pyrrolidine and 1,4-dioxa-8-azaspiro[4,5]decane (DASD) give the corresponding new fully substituted phosphazenes (14 and 16). Unexpectedly, the reactions of 23 and 24 with pyrrolidine result in only geminal crypta phosphazenes (26 and 27). The solid-state structures of 16 and 22 have been determined by X-ray diffraction techniques. The relative inner hole-size of the macrocycle in the radii of 22 is 1.27 A. The relationship between the exocyclic NPN (alpha') and endocyclic (alpha) bond angles for spiro-crypta phosphazenes and exocyclic OPN (alpha') bond angles for spiro-ansa-spiro- and spiro-bino-spiro-phosphazenes with 31P NMR chemical shifts of NPN and OPN phosphorus atoms, respectively, have been investigated. The structures of 10, 14, 16, 19, 21, 22, and 25-27 have also been examined by FTIR, 1H, 13C, and 31P NMR, HETCOR, MS, and elemental analyses. The 31P NMR spectra of 10, 21, 22, and 25 indicate that the compounds have anisochrony. In compounds 16 and 22, the spirocyclic nitrogen atoms have pyramidal geometries resulting in stereogenic properties.     

Synthesis of New Pyrroline Nitroxides with Ethynyl Functional Group

3-Substituted and 3,4-disubstituted pyrroline nitroxides containing an ethynyl group or two ethynyl groups were achieved by the reaction of a paramagnetic aldehydes with dimethyl (1-diazo-2-oxopropyl)phosphonate (Bestmann–Ohira reagent). The new compounds containing an ethynyl group were found to be useful building blocks in Sonogashira coupling, cyclization, and cycloaddition reactions producing potentially “azido-specific” cross-linking spin labels, paramagnetic ligands, and polyradical scaffolds.     

The conformational structures of defect-containing chains in the crystalline regions of isotactic polypropylene

Calculations were performed to assign defect-resonance patterns observed in solid-state ¹³C NMR spectra obtained from the crystalline regions of isotactic polypropylene. The spectral features of interest are associated with stereo, regio, and comonomer-type defects, which can typically be found in metallocene-synthesized polymers. The calculations were carried out as follows: a model of the crystalline region of defect-free isotactic polypropylene was constructed from available X-ray data corresponding to the α-lattice. A series of irregularities including ethylene comonomer, stereo-mrrm, regio 2,1-erythro, and butylene-comonomer defects were introduced one at a time at various positions in a specific stem occupying a central position in the model crystallite. Low-lying conformations were then obtained from simulated annealing calculations that were initiated from these structures. Finally, quantum mechanical calculations were performed on the representative segments of the defect-containing chains excised from the annealed crystallites and the calculated chemical shifts were compared to the observed resonances. The results of the calculations were used as a basis for interpreting the NMR intensities of defect-related resonances in terms of the partitioning of defects and to help establish the conformational structures of the defect-containing stems.     

Diastereoselective Nucleophilic Ring‐Opening Reactions of 2,6‐Diazasemibullvalenes for the Synthesis of Diverse Functionalized Δ1‐Bipyrroline Derivatives

Nucleophilic ring‐opening reactions of 2,6‐diazasemibullvalenes (NSBVs) were investigated. Different types of nucleophile (alcohols, phenols, thiols, carboxylic acids, water, enols, amines, indoles, metal‐halide salts, sodium azide, organozinc compounds, lithium alkynethiolate, and sulfoxonium ylides) were used to afford diverse functionalized Δ¹‐bipyrroline derivatives in good yields with high regio‐ and diastereoselectivity. Most of the reactions featured milder conditions and higher reactivity relative to those for common aziridine derivatives, probably because of the rigid ring system and substitution patterns of NSBVs.     

Studies on the structure behavior of triphenyldichlorophosphorane in different solvents

Triphenyldichlorophosporane, which was prepared according to Appel reaction, was an efficient reagent for alkyl halide synthesis by virtue of having two replaceable groups on "pentavalent" phosphorus. The reaction of triphenylphosphine with hexachloroethane was investigated in different solvents and 31P NMR traced the processes of these reactions. As results, it was found that there was similar high coordinated phosphorus species formed in aromatic solvents and in ring ether type solvents, which had large 1J(P-C) (about 140 Hz) according to 13C NMR experiments. It is indicated that, for some solvent such as benzene or dioxane, solvent molecules might be locked in the high coordinated phosphorus compounds, which in turn would affect the triphenyl groups situated at the equatorial position.     

Microbial transformations. Part 7 (1) Biohydroxylation of bornylamide derivatives by the fungus beauveria sulfurescens

The biohydroxylation of various amide derivatives of norbornane and of camphane have been studied, in order to explore the possible influence of the amide group configuration and substitution upon the regio, the stereo and the enantioselectivity of the process. The results obtained indicate that, for two cases out of the three, the variation of configuration of the amide group has no influence on the hydroxylatian selectivity. However, it appears that, in the case of the endo N-methylated amide derived from camphane, the results are completely different. In particular, we observe partial resolution of the starting racemic compound, due to different regioselectivities occuring in the hydroxylation of each of the two enantiomers.     

NMR shielding calculations across the periodic table: diamagnetic uranium compounds. 2. Ligand and metal NMR

In this and a previous article (J. Phys. Chem. A 2000, 104, 8244), the range of application for relativistic density functional theory (DFT) is extended to the calculation of nuclear magnetic resonance (NMR) shieldings and chemical shifts in diamagnetic actinide compounds. Two relativistic DFT methods are used, ZORA ("zeroth-order regular approximation") and the quasirelativistic (QR) method. In the given second paper, NMR shieldings and chemical shifts are calculated and discussed for a wide range of compounds. The molecules studied comprise uranyl complexes, [UO(2)L(n)](+/-)(q); UF(6); inorganic UF(6) derivatives, UF(6-n)Cl(n), n = 0-6; and organometallic UF(6) derivatives, UF(6-n)(OCH(3))(n), n = 0-5. Uranyl complexes include [UO(2)F(4)](2-), [UO(2)Cl(4)](2-), [UO(2)(OH)(4)](2-), [UO(2)(CO(3))(3)](4-), and [UO(2)(H(2)O)(5)](2+). For the ligand NMR, moderate (e.g., (19)F NMR chemical shifts in UF(6-n)Cl(n)) to excellent agreement [e.g., (19)F chemical shift tensor in UF(6) or (1)H NMR in UF(6-n)(OCH(3))(n)] has been found between theory and experiment. The methods have been used to calculate the experimentally unknown (235)U NMR chemical shifts. A large chemical shift range of at least 21,000 ppm has been predicted for the (235)U nucleus. ZORA spin-orbit appears to be the most accurate method for predicting actinide metal chemical shifts. Trends in the (235)U NMR chemical shifts of UF(6-n)L(n) molecules are analyzed and explained in terms of the calculated electronic structure. It is argued that the energy separation and interaction between occupied and virtual orbitals with f-character are the determining factors.     

Deprotonation-substitution reactions of cyclic methylphenylphosphazenes: synthesis and structures of nongeminal P-ethyl,P-phenyl cyclotriphosphazenes

The deprotonation-substitution reactions of both the cis and trans isomers of nongeminally substituted [(Me)(Ph)P=N](3) were investigated. Treatment of the trans isomer, 1, with 3 equiv of n-BuLi followed by 3 equiv of MeI gave only nongeminal trans-[(Et)(Ph)P=N](3), 3, while the same reaction sequence on cis-[(Me)(Ph)P=N](3), 2, gave a mixture of nongeminal di- and trisubstitution products, cis-Et(2)MePh(3)P(3)N(3), 4, and cis-Et(3)Ph(3)P(3)N(3), 5. These trimers were separated by column chromatography. No changes in the stereochemistry of the rings occurred during these reactions. Compound 4 was also prepared using 2 equiv of the reactants and was then converted to 5 by treatment with a single equivalent of BuLi and MeI. Thermal analysis of the new cyclic trimers indicates that ring-opening polymerization does not occur and that sublimation occurs at ca. 300 degrees C. The structures of 4 and 5, obtained by X-ray diffraction, illustrate the basketlike shape of these molecules with an aromatic bowl formed by the phenyl rings on the top rim, while the structure of 3 clearly shows the trans orientation of the substituents. Crystal data for trans-Et(3)Ph(3)P(3)N(3), 3, at 20 degrees C are as follows: C(24)H(30)N(3)P(3) monoclinic, a = 14.273(2) A, b = 9.370(2) A, c = 19.600(3) A, beta = 107.16(1) degrees, P2(1/n), Z = 4. Crystal data for cis-Et(2)MePh(3)P(3)N(3), 4, at 20 degrees C are as follows: C(23)H(28)N(3)P(3), triclinic, a = 10.276(2) A, b = 10.699(2) A, c = 11.925(2) A, alpha = 72.07(2) degrees, beta = 73.79(1) degrees, gamma = 85.87(1) degrees, P1, Z = 2. Crystal data for cis-Et(3)Ph(3)P(3)N(3), 5, at 20 degrees C are as follows: C(24)H(30)N(3)P(3) monoclinic, a = 29.488(2) A, b = 9.8391(1) A, c = 21.172(2) A, beta = 126.30(1) degrees, C2/c, Z = 8.     

C- and N-Substituted Phosphorus(III) Derivatives of Azomethines

Abstract

The reactions of halogenides of P(III) acids with lithium derivatives of azomethines depending on the substituents at the phosphorus atom, the structure of azomethines and conditions of the reaction were studied. A method for synthesizing tile C- and N-phorphorus(III) substituted azomethines was proposed:     

Stereoselective preparation of (RP)-8-hetaryladenosine-3',5'-cyclic phosphorothioic acids

Cyclic adenosine monophosphate (cAMP) has been converted into its 8-bromo derivative and 2'O-TBDMS protected before activation of the phosphoric acid moiety with a reagent generated in situ from oxalyl chloride and DMF. Further reactions with primary amines furnished corresponding phosphoramidates with high stereoselectivity at the phosphorus atom. Cross-coupling reactions with the 8-bromopurine yielded 8-hetaryl derivatives. X-Ray analyses showed the amidates to possess the (S(P))-configuration. Carbon disulfide effected thiylation under strongly basic conditions stereospecifically provided the (R(P))-phosphorothioic acids.     

Reactions of Tris(Perfluoroalkyl)Difluorophosphoranes and Their Derivatives with Nucleophilic Reagents

Abstract

This paper is concerned with the reactions of (R_f)₃PF₂ and (R_f)₃PO with N-, 0-, C-nucleophiles and fluoride ion. Either the replacement of one or two perfluoroalkyl radicals by different functional groups or the addition of reagent to electrophilic phosphorus occurs. These phosphinic oxides and phosphoranes readily add fluoride-ion with the expansion of phosphorus coordination: the former produces phosphoranes OP a new type (R_f)₃P(F)O_?Cs₊, while the latter stable substituted fluorophosphates of general formula M ₊[(R_f)₃ PF₃]_?. Based on these salts it was possible to synthesize aryldiazonium tris(perfluoroalkyl)trifluorophosphates, whose thermal decomposition leads to the formation of substituted fluorobenzenes with high yields. The reaction is a convenient modification of the Shieman methd. The approaches of the synthesis of phosphoranes containing simultaneously both perfluoroalkyl groups and nonfluorin-ated radicals are developed due to the reactions of tris-(perf luoroalkyl)dif luorophosphoranes with the lithium-organic compounds. The replacement of either fluorine atom or perfluoroalkyl radical by the nonfluorinated group depends on the lithium reagent nature: