Synthesis of both RP and SP enantiomers of unsymmetrical methylphosphonates based on a new approach utilizing a P-ester bond with α-hydroxyacids

Condensation of methyl methylphosphonochloridate with the dilithium salt of 2-methyllactic acid gave P-racemic methylphosphonates which unexpectedly contained two units of α-hydroxyacid linked via carboxylic ester bond. The racemic mixture was chromatographically separated via diastereomeric salts with quinine or cinchonine to give, based on the X-ray analysis, pure (R_P)-(+) and (S_P)-(−) enantiomers. Both enantiomers were immobilized on the ArgoGel^®–OH solid support. Condensation of methyl methylphosphonochloridate with α-hydroxyacid methyl esters [2-methyllactate, (S_C)-(−)-lactate, methyl (S_C)-(+) and (R_C)-(−)-mandelates] gave chromatographically inseparable 1:1 mixtures of diastereomers in 63–69% yields. A basic hydrolysis of the latter resulted in a selective and unexpected cleavage of the P–OMe group in a quantitative yield [(S_C)-(+) and (R_C)-(−)-mandelates, (S_C)-(−)-lactate] or simultaneous cleavages of P–OMe and C(O)OMe groups (2-methyllactate).     

Shape- and stereo-selective esterase activities of cross-linked polymers imprinted with a transition-state analogue for the hydrolysis of amino acid esters

Various cross-linked (with N,N′-ethylene (C₂), butylene (C₄), hexamethylene (C₆), or decamethylene (C₁₀)-bisacrylamide) polymer catalysts containing l-histidine and quaternary trimethylammonium groups were imprinted with a racemic transition-state analogue of phenyl 1-benzyloxycarbonyl-3-methylpentylphosphonate for the hydrolysis of p-nitrophenyl N-(benzyloxycarbonyl)-l (or d)-leucinate (Z-l (or d)-Leu-PNP). Among these polymer catalysts, N,N′-C₄-bisacrylamide-cross-linked polymer catalyst, which was copolymerized with styrene monomer, exhibited the notable substrate-stereospecificity for the Z-l-Leu-PNP hydrolysis among the hydrolyses of enantiomeric l (or d)-N-protected (such as tert-butyloxycarbonyl (Boc-), acetyl (C₂-), decanoyl (C₁₀-) or benzyloxycarbonyl (Z-)) amino acid (Leu, Ala, or Phe) p-nitrophenyl esters in 10 vol.% MeCN-Tris buffer (pH 7.15) at 30°C.     

Mono-, di-, and tetra-aurated derivatives of barbituric acid,including a new type of polynuclear gold compound. Crystal structure of 1,3-bis(triphenylphosphinegold)-5,5-diethylbarbituric acid

Reaction of barbituric acid (2,4,6-pyrimidinetrione) or its derivatives with LAuCl (L = triphenylphosphine) gave 3-LAu-5,5-diethyl-, 1,3-(L'Au)₂-5,5-diethyl- (L′ = L or L′ = Cy₃P), 1,3-dimethyl-5,5-bis(LAu)-, or 1,3,5,5-tetrakis-(LAu)barbituric acid, which were characterized as N-, N,N′-, C,C′-, or N,N′,C,C-gold derivative,s respectively, by IR, ¹H, ¹³C and ³¹P NMR spectroscopy. In the case of 1,3-(LM)(L″M)-5,5-diethylbarbituric acid compounds with M = gold and L″ either Cy₃P, Ph₃As, or (4-tolyl)₃P, or ML = ML″ = HgMe were prepared. An X-ray diffraction study of 1,3-(LAu)₂-5,5-Et₂-pyrimidin-2,4,6-trione · 3C₆H₆ revealed that (a) the heterocyclic ring is planar, (b) there is no inter- or intra-molecular Au ⋯ Au interaction, and (c) the coordination around each gold atom is approximately linear (PAuN 178.3(4)°, with AuN 2.022(12) and AuP 2.233(5) Å. The molecular parameters are compared with those for barbituric acid and other barbiturates.     

Synthesis and solution properties of sulfate-type hybrid surfactants with a benzene ring

Nine novel sulfate-type hybrid surfactants, C_mF_2m+1C₆H₄CH(OSO₃Na)C_nH_2n+1 (FmPHnOS: m=4, 6, 8; n=3, 5, 7; C₆H₄: p-phenylene), with a benzene ring in their molecules were synthesized. Alkanoyl chlorides were allowed to react with iodobenzene in the presence of aluminum chloride to give the corresponding aromatic ketones. The reaction of the ketones with perfluoroalkyl iodides yielded 1-[4-(perfluoroalkyl)phenyl]-1-alkanones as intermediates. The intermediates were allowed to react with methanol in tetrahydrofuran in the presence of sodium borohydride to yield 1-[4-(perfluoroalkyl)phenyl]-1-alkanols. The desired hybrid surfactants were obtained by the reaction of 1-[4-(perfluoroalkyl)phenyl-1-alkanols with sulfur trioxide/pyridine complex in pyridine and by the subsequent neutralization of the products with sodium hydroxide solution. When compared with the conventional hybrid surfactants, C_mF_2m+1C₆H₄COCH(SO₃Na)C_nH_2n+1 (FmHnS: m=4, 6; n=2, 4, 6; C₆H₄: p-phenylene), the new hybrid surfactants thus synthesized were found to have a comparable ability to lower the surface tension of water and a high hydrophilicity. The cmc of FmPHnOS obeyed Kleven’s rule and their occupied areas per molecule increased with increasing m and n with the values between 0.66 and 1.05 nm². The aggregation number for FmPHnOS micelles ranged from 6 to 45 and the hydrodynamic radius of the micelles was in the range of 1.4-3.1 nm.     

Bi(III) Catalysed O-acylative cleavage of 2,5-dimethyltetrahydrofuran: a substrate dependent borderline mechanism

The Bi(III) catalysed O-acylative cleavage of cis- and trans-2,5-dimethyltetrahydrofuran 4 with AcCl, BzCl or i-PrCOCl is stereochemically consistent with the operation of a concerted process (A_ND_N), which proceeds via a stabilised carbocation or ‘loose’ S_N2 transition state. However, the O-acylative cleavage of cis-2,5-dimethyltetrahydrofuran 4 with sterically demanding electrophiles such as t-BuCOCl, appears to be stereochemically consistent with the alternative S_N1 (D_N+A_N) pathway. The apparent merging of mechanistic pathways is rationalised by the participation of a strained acyloxy cation.     

Application of axially dissymmetric ligand recoverable with fluorous solvent as a chiral auxiliary

(Ra)-(R)₂-2,2′-Bis(1-hydroxy-1H-perfluorooctyl)biphenyl ((Ra)-(R)₂-1c), which is an axially dissymmetric ligand with two chiral centers, works as a good chiral auxiliary for asymmetric aldol reaction. Thus, the reaction of monopropanoyl ester of 1c (2) with benzaldehyde in the presence of triethylamine and titanium(IV) chloride gave (2R),(3S)- and (2R),(3R)-3-hydroxy-2-methyl-3-phenylpropanoic acid esters (3a) in an approximate ratio of 4:1 in a total high yield. This result shows that stereoselectivity at 2-position is quite high, while that at 3-position is moderate. Both isomers were easily separated by column chromatography. Methanolysis of the separated isomers gave nearly quantitative recovery of 1c by extraction with a fluorous solvent without any loss of ee, while methyl (2R),(3S)- or (2R),(3R)-3-hydroxy-2-methyl-3-phenylpropanoates were obtained by CH₂Cl₂ extraction quantitatively in >99% ee. Aldol reaction of 2 with various aldehydes gave similar results.     

2-(2-Hydroxyaryl)cinnamic amides: a new class of axially chiral molecules

The syntheses of several differently substituted amides formally derived from a chiral amine, either E-2-(2-hydroxyphenyl)cinnamic acid or both E- and Z-2-(2-hydroxynaphthyl)cinnamic acid, are reported. These molecules display a restricted rotation about the C₂-C_aryl bond. The barriers to rotation about the C₂-C_aryl bond were measured by the dynamic ¹H NMR and were found to vary between 11.8 and 24.5 kcal mol⁻¹, depending on the substitution. In particular, E-2-(2-hydroxynapthyl)cinnamic amides, displayed a high barrier to rotation (ΔG_c^‡=24.4 kcal mol⁻¹) and could be isolated in both diastereomerically pure forms at room temperature. The X-ray structure of one E-2-(2-hydroxynapthyl)cinnamic amide, was resolved, enabling for the determination of the absolute configuration of the chiral axis (aR).     

Synthesis,characterization, and structures of arylaluminum reagents and asymmetric arylation of aldehydes catalyzed by a titanium complex of an N-sulfonylated amino alcohol

A series of phenylaluminum reagents AlPh_xEt_3?x(L) (x = 1–3) containing adduct ligand L [Et₂O, THF, OPPh₃, or 4-dimethylaminopyridine (DMAP)] were synthesized and characterized. NMR studies showed that AlPh_xEt_3?x(L) (x = 1 or 2) exists as an equilibrium mixture of 3–4 species in solution. Solid-state structures of the phenylaluminum reagents reveal a distorted tetrahedral geometry. Asymmetric additions of phenylaluminum to 2-chlorobenzaldehyde were examined employing a titanium(IV) complex [TiL¹(OPrⁱ)₂]₂ 10 (H₂L¹ = (1R,2S)-2-(p-tolylsulfonylamino)-1,3-diphenyl-1-propanol) as a catalyst precursor. It was found that the adduct ligand L had a strong influence on the reactivity and the enantioselectivity in asymmetric phenyl additions to aldehydes. The phenylaluminum reagents with OPPh₃ or DMAP were unreactive toward aldehydes, and AlPh₃(THF) was found to be superior to AlPh₃(OEt₂) or AlPhEt₂(THF). Asymmetric aryl additions of AlAr₃(THF) to aldehydes employing a loading of 5 mol % titanium(IV) complex 10 with a strategy of a slow addition of the aldehydes over 20 min were conducted, and the reactions produced optically active secondary alcohols in high yields with excellent enantioselectivities of up to 94% ee.     

Ruthenium carborane complexes: a relationship between the structure, electrochemical properties, and reactivity in catalysis of polymerization processes

The ruthenacarborane complexes of the exo-nido- and closo-structure, namely, diamagnetic exo-nido-5,6,10-[RuCl(PPh₃)₂]-5,6,10-(μ-H)₃-10-H-7,8-(CH₃)₂-7,8-C₂B₉H₆, 3,3-[Ph₂P(CH₂) _n PPh₂]-3-H-3-Cl-closo-3,1,2-RuC₂B₉H₁₁ (n = 4, 5), paramagnetic 3,3-[Ph₂P(CH₂) _n PPh₂]-3-Cl-closo-3,1,2-RuC₂B₉H₁₁ (n = 2–5), and their some ortho-phenylenecycloboronated derivatives, were studied by cyclic voltammetry. All chelate closo-complexes are characterized by reversible redox transitions, while the exo-nido-complex is liable to irreversible oxidation. Shortening of the methylene link in the diphosphine ligand of closo-ruthenacarboranes and/or the introduction of ortho-phenylenecycloboronated moieties and methyl substituents to the carbon atoms of the {C₂B₉} ligand lead to a decrease in the redox potential and electron density redistribution to the metal atom. A comparison of the experimental results on methyl methacrylate polymerization in the presence of the catalytic systems based on the studied metallacarboranes with the data on their electrochemical characteristics suggests that the efficiency of using the ruthenium complexes as catalysts is mainly determined by steric factors.     

Heck reactions of 2-substituted enol ethers with aryl bromides catalysed by a tetraphosphine/palladium complex

cis,cis,cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C₃H₅)]₂ efficiently catalyses the Heck reaction of β-substituted enol ethers with aryl bromides. Employing β-methoxystyrene, 3-ethoxyacrylonitrile or methyl 3-methoxyacrylate, the regioselective α-arylation of these enol ethers was observed in all cases, and mixtures of Z and E isomers were generally obtained, which in many cases yielded a single ketone product after acid treatment. The stereoselectivity of this reaction depends on steric and electronic factors, and better stereoselectivities in favour of Z isomers were observed with electron-rich or sterically congested aryl bromides. Better yields were obtained for this reaction with electron-rich or sterically congested aryl bromides than with electron-poor aryl bromides. This observation suggests that with these β-substituted enol ethers the rate-limiting step of the catalytic cycle is not the oxidative addition of the aryl bromide to the palladium complex.     

Synthesis of N-acetyl-3,3a,4,8b- and -1,3a,4,8b-tetrahydrocyclopenta[b]indoles from N- and 2-(cyclopent-2-en-1-yl)anilines

Reactions of 2-bromo-N-(cyclopent-2-en-1-yl)-4-methylaniline and N-(cyclopent-2-en-1-yl)-2-iodo-4,6-dimethylaniline with acetyl bromide in the presence of potassium carbonate gave mixtures of syn and anti atropisomers of the corresponding N-acetyl derivatives at ratios of 1: 1 and 3: 2 respectively. Heating of these mixtures in toluene in the presence of Pd(OAc)₂, PPh₃, Et₃N, and K₂CO₃ (KOAc) afforded mixtures of isomeric N-acetyl-7-methyl-3,3a,4,8b- and -1,3a,4,8b-tetrahydrocyclopenta[b]indoles at a ratio of 3: 1 or N-acetyl-5,7-dimethyl-3,3a,4,8b- and -1,3a,4,8b-tetrahydrocyclopenta[b]indoles at a ratio of 2: 3. N-Acetyl-3,3a,4,8b-tetrahydrocyclopenta[b]indole was found to undergo thermal isomerization into N-acetyl-1,3a,4,8btetrahydrocyclopenta[b]indole.     

Synthesis of eleven-membered carbocycles via a homo-Cope type of five-carbon ring expansion reaction utilized β-(hydroxymethyl)allylsilane

Eleven-membered carbocycles were synthesized from six-membered compounds fitted with a β-(hydroxymethyl)allylsilane unit via the title reaction. Namely, trans- and cis-(E)-2-(trimethylsilylmethyl)-3-(2-vinylcyclohex-1-yl)prop-2-en-1-ol were treated with Tf₂O in CH₂Cl₂ in the presence of 2,6-lutidine to afford (1E)-3-methylenecycloundeca-1,6-diene in good yield. The geometry of the product was shown to depend upon the trans- and cis-substitution pattern on the cyclohexane ring of the substrates; i.e. trans-isomer afforded (6E)-product exclusively and cis-isomer afforded the mixture of (6E)- and (6Z)-product in 1:2 ratio. The (Z)-substrate with respect to allylsilane moiety afforded the same ring expansion product, however, the yield was lower than the reaction with the (E)-substrate. The substrates bearing t-butyl or benzyloxy substituents on the cyclohexane ring also afforded the product analogously, indicating that the reaction depends upon the conformation of the substrate. On the other hand, the substrate bearing isopropenyl group instead of a simple vinyl group did not afford the ring expansion product but produced bicyclo[5.4.0]undecane via the ene reaction.     

High asymmetric induction using a diastereomeric mixture of axially dissymmetric ligands

We have reported that our new axially dissymmetric ligand with two chiral centers, (R_a)-2,2′-bis[(R)-1H-1-hydroxyperfluorooctyl]biphenyl ((R_a)-(R)₂-1c, or tentatively called as (R_a)-(R)₂-PFCAB-7), worked as a good asymmetric inducer for the reaction of benzaldehyde with diethylzinc. Now, a mixture of (R_a)-(R)₂- and (S_a)-(R)₂-PFCAB-7 even in 1:4 ratio (−60% de) was found to give nearly the same asymmetric induction as pure (R_a)-(R)₂-PFCAB-7 of the corresponding molar percents. This result suggests that both isomers do not form complex and that (R_a)-(R)₂-PFCAB-7 accelerates the reaction and induces high asymmetry, while (S_a)-(R)₂-1c does not accelerate the reaction significantly and does not induce asymmetry at all. This ligand of low ee, (R_a)-(R)₂-PFCAB-7 of 20% ee, did not show appreciable asymmetric amplification, suggesting no formation of heterochiral complex.     

Binap-gold(I) trifluoroacetate as a bifunctional catalyst for the synthesis of chiral prolines through 1,3-dipolar cycloaddition of azomethine ylides

Highly enantioselective 1,3-dipolar cycloadditions of amino acid-derived azomethine ylides with alkenes have been performed, for the first time, under gold-catalysis using (S_a)- or (R_a)-Binap-gold(I) trifluoroacetate complexes, with the cationic Binap-gold acting as a Lewis acid and the counteranion as a base. Maleimides and trans-1,2-bis(phenylsulfonyl)ethylene were reacted with imino esters at room temperature in the absence of a base to afford, in very good yields, the corresponding polysubstituted prolines with total endo-diastereoselection and higher enantioselectivities than the Binap-silver trifluoroacetate complex.     

MM3 force field prediction of the enantioselective preference in the asymmetric synthesis of a chiral 2-cyclohexen-1-ol using a chiral lithium amide reagent

Enantioselective preference in the asymmetric synthesis where cyclohexene oxide is transformed enantioselectively to chiral (S)- or (R)-2-cyclohexen-1-ol by the reaction with the appropriate chiral lithium amide reagent has been evaluated theoretically using the MM3 force field. The plausible possible structures for each precursor (reaction intermediate complex) leading to a (S)- or (R)-2-cyclohexen-1-ol have been optimized with the extended MM3 force field applicable to the lithium amide functional group, and the populations of their (S)- or (R)-reaction intermediate complexes at an ambient temperature (298 K) were calculated. The initial structure for evaluating the reaction intermediates of this asymmetric synthesis was constructed on the basis of the optimized ab initio transition state structure (MP2/6-31+G^∗) comprising lithium amide LiNH₂ and propene oxide. To the thus obtained transition state structure composed of LiNH₂ and propene oxide, the other remaining Cartesian coordinates for the actual reaction intermediates composed of the chiral lithium amides and cyclohexene oxide were added to make the reaction intermediate structure. The conformational search for the reaction intermediate has been carried out by using the Stochastic search Algorithm, and the optimized geometries and their conformational energies (steric energies) have been calculated by the MM3 force field. The populations calculated from the conformational energies of the reaction intermediate leading to the (S)- or (R)-2-cyclohexen-1-ol were shown to be linearly well correlated with the experimentally reported enantiomer excess (% ee) values. The critical factors to control the enantioselectivity were investigated on the basis of the optimized structures of the reaction intermediate complexes. The MM3 force field approach was shown to be applicable to the theoretical evaluation of the enantioselectivity and be useful for designing a new functional chiral lithium amide reagent for the asymmetric synthesis.     

Thermodynamic study of the liquid Fe-S system by use of a drop calorimeter

Heat contents of the Fe-S system were measured with a drop calorimeter in the sulfur composition range X_s = 0.380–0.500 (FeS) and in the temperature range 942–1506 K to construct an (H_T - H_298.15)-temperature-composition ternary diagram. By use of a thermodynamic analysis method, the mixing free energy, enthalpy and entropy of the liquid Fe-S mixtures were determined at 1473 and 1523 K, based on the measured heat contents. The partial molar free energies (activity of iron and partial pressure of diatomic sulfur) agreed well with the literature values, suggesting the applicability of the thermodynamic analysis method for liquid mixtures with semi-metals or chalcogen.     

Creation of a stereoselective solid surface by self-assembly of a chiral metal complex onto a nano-thick clay film

A stereoselective solid surface has been created by the self-assembly of a chiral osmium complex, λ-[Os(phen)₃](ClO₄)₂ (phen=1,10-phenanthroline), onto a single layered clay film deposited on an indium tin oxide (ITO) electrode; the Os^II–Os^III redox couple mediates the electrochemical oxidation of chiral 1,1^′-2-binaphthol in a stereoselective way or the S-isomer is oxidized at 1.4 times higher rate than the R-isomer.     

Synthesis of acetals containing a primary amino group

Amino acetals of the general formula MeCH(OR)(OXNH₂) (R = Et, Bu, X = CH₂CH₂, CH₂CH₂CH₂, CH₂CMe₂) were synthesized in 53?C91% yield by acid-catalyzed reaction of N-(2-hydroxyethyl)-, N-(3-hydroxypropyl)-, and N-(2-hydroxy-1,1-dimethylethyl)-2,2,2-trifluoroacetamides with vinyl ethers, followed by removal of the trifluoroacetyl protection by alkaline hydrolysis.     

A theoretical study on the strength of multiple metal-metal bonds in binuclear complexes and transition-metal dimers by a non-local density functional method

The strength of multiple metal-metal bonds in the metal dimers M₂ (M = Cr, Mo or W) and binuclear complexes M₂(OH)₆ (M = Cr, Mo or W), M₂Cl₄(PH₃)₄ M = V, Cr, Mn, Nb, Mo, Tc, Ta, W or Re) has been studied by a non-local density functional theory. The method employed here provides metal-metal bond energies [D(M-M)] in good accord with experiments for Cr₂ and Mo₂, and predicts that W₂ of the three dimers M₂ (M = Cr, Mo or W) has the strongest metal-metal bond with D(W-W) = 426 kJ mol⁻¹ and R(W-W) = 2.03 Å. Among the binuclear complexes studied here we find the 3d elements to form relatively weak metal-metal bonds (40–100 kJ mol⁻¹), compared to the 4d and 5d elements with bonding energies ranging from 250 to 450 kJ mol⁻¹. The metal-metal bond for a homologous series is calculated to be up to 100 kJ mol⁻¹ stronger for the 5d complex, than for the 4d complex. An energy decomposition of D(M-M) revealed that the σ-bond is somewhat stronger than each of the π-bonds, and one order of magnitude stronger than the δ-bond. For the same transition metal we find D(M-M) to be larger for M₂(PH₃)₄Cl₄ (M = Cr, Mo or W) than for M₂(OH)₆ (M = Cr, Mo or W), and attribute this to a stronger π-interaction in the former series. While many of the findings here are in agreement with previous HFS studies, the order of stability D(3d-3d) « D(4d-4d) < D(5d-5d) differs from the order D(3d-3d) « D(5d-5d) < D(4d-4d) obtained by the HFS method, and the present method provides in general more modest values for D(M-M) than the HFS scheme.     

Coupling reactions of aryl bromides with 1-alkynols catalysed by a tetraphosphine/palladium catalyst

cis,cis,cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C₃H₅)]₂ system catalyses efficiently the coupling reactions of aryl halides with a variety of alkynols such as propargyl alcohol, but-1-yn-4-ol, pent-1-yn-5-ol or hex-1-yn-6-ol. The catalyst can be used at low loading. Higher reaction rates were observed in the presence of but-1-yn-4-ol, pent-1-yn-5-ol or hex-1-yn-6-ol than with propargyl alcohol. The protection of the alcohol functions as an ether or a silyloxy group led generally to similar or better results than the reactions performed with the unprotected alcohols.