A new copper(I)-tetrahydrosalen-catalyzed asymmetric Henry reaction and its extension to the synthesis of (S)-norphenylephrine

A new chiral hydrogenated salen catalyst has been developed for the asymmetric Henry reaction which produces the expected products in moderate to high yields (up to 98 %) with excellent enantioselectivities (up to 96 % ee). A variety of aromatic, heteroaromatic, enal, and aliphatic aldehydes were found to be suitable substrates in the presence of hydrogenated salen 1 f (10 mol %), (CuOTf)(2)C(7)H(8) (5 mol %), and 4 A molecular sieves. This process is air-tolerant and easily manipulated with readily available reagents, and has been successfully extended to the synthesis of (S)-norphenylephrine in 67 % overall yield, starting from commercially available m-hydroxybenzaldehyde. Based on experimental investigations and MM+ calculations, a possible catalytic cycle including a transition state (8 or A) has been proposed to explain the origin of reactivity and asymmetric inductivity.     

Synthesis of C1-symmetric chiral secondary diamines and their applications in the asymmetric copper(II)-catalyzed Henry (nitroaldol) reactions

A small library of C(1)-symmetric chiral diamines (L1-L9) was constructed via condensing exo-(-)-bornylamine or (+)-(1S,2S,5R)-menthylamine with various Cbz-protected amino acids. Among them, ligand L1/CuCl(2)·2H(2)O complex (2.5 mol %) shows outstanding catalytic efficiency for Henry reaction between a variety of aldehydes and nitroalkanes to afford the expected products in high yields (up to 98%) with excellent enantioselectivities (up to 99%) and moderate to good diastereoselectivities (up to 90:10). This process is air- and moisture tolerant and has been applied to the synthesis of (S)-2-amino-1-(3,4-dimethoxyphenyl)ethanol (9), a key intermediate for (S)-epinephrine and (S)-norepinephrine. On the basis of HRMS and X-ray diffraction analysis of the L1/CuCl(2) complex, a transition-state model was proposed to explain the origin of asymmetric induction. The low catalyst loading, excellent yields and enantioselectivities, inexpensive copper salt, and mild reaction conditions make our catalytic system to be practically useful.     

Chiral binaphthylthiophosphoramide-cu(I)-catalyzed asymmetric addition of diethylzinc to N-sulfonylimines

In the presence of a catalytic amount of chiral binaphthylthiophosphoramide L2 (6 mol %) and Cu(I) (3 mol %), the asymmetric addition of diethylzinc to N-sulfonylimines could be achieved in good yields with moderate to high ee (63-93% ee) at 0 degrees C in toluene. A novel chiral binaphthylthiophosphoramide ligand system for this asymmetric addition reaction has been explored.     

Syntheses,toxicity and biodistribution of CO‐releasing molecules containing M(CO)5 (M = Mo,W and Cr)

A series of CO‐releasing molecules M(CO)₅ L (M = Mo, W and Cr), ( 1 , 2 , 3 , L = glycine methyl ester; 4 , 5 , 6 , N‐methylimidazole; 7 , 8 , 9 , 2‐aminopyridine; 10 , 11 , 12 , 3‐aminopyridine; 13 , 14 , 15 , 4‐aminopyridine), were synthesized. All complexes have been characterized by NMR, IR and electrospray ionization mass spectroscopy; the octahedral structures of 14 and 15 were also established by X‐ray crystallography. Furthermore, all complexes were evaluated for toxicity, pharmacokinetics and metabolic processes. Cytotoxic effects on the proliferation of fibroblast cell line were assayed by MTT. Among the complexes, Mo complex 1 showed the lowest cytotoxicity (IC₅₀ = 597 µmol l^?1) and W complex 2 showed a remarkable toxic effect, with IC₅₀ = 52 µmol l^?1. With the same ligand, the toxic effects of the complexes increase in the order of metal element W < Cr < Mo. For the same central metal element, the complexes containing imidazole showed lower toxic effects than those containing amino acid ester or aminopyridine. In accordance with the results from cytotoxicity, the complexes also showed corresponding toxic effects in animal models. The biodistributions of the complexes were established by inductively coupled plasma–atomic emission spectroscopy, measuring metal in tissues and organs. The results show that the complexes were gradually absorbed and unevenly distributed in vivo. The complexes containing imidazole entered tissues and organs faster than those containing amino acid ester. The complexes containing W atom were absorbed and distributed more slowly than those containing Mo or Cr atoms. Copyright © 2014 John Wiley & Sons, Ltd.     

Chiral phosphane alkenes (PALs): simple synthesis, applications in catalysis, and functional hemilability

A simple synthesis of a chiral phosphane alkene (PAL) involves: 1) palladium-catalyzed Suzuki coupling of 10-bromo-5H-dibenzo[a,d]cyclohepten-5-ol (1) with phenylboronic acid to give quantitatively 10-phenyl-5H-dibenzo[a,d]cyclohepten-5-ol (2); 2) reaction of 2 with Ph(2)PCl under acidic conditions to give a racemic mixture of the phosphane oxide (10-phenyl-5H-dibenzo[a,d]cyclohepten-5-yl)diphenylphosphane oxide ((Ph)troppo(Ph), 3), which is separated into enantiomers by using high-pressure liquid chromatography (HPLC) on a chiral column; 3) reduction with trichlorosilane to give the enantiomerically pure phosphanes (R)- and (S)-(10-phenyl-5H-dibenzo[a,d]cyclohepten-5-yl)diphenylphosphane ((Ph)tropp(Ph), 4). This highly rigid, concave-shaped ligand serves as a bidentate ligand in Rh(I) and Ir(I) complexes. Catalysts prepared from [Rh(2)(mu(2)-Cl)(2)(C(2)H(4))(4)] and (S)-4 have allowed the efficient enantioselective 1,4-addition of arylboronic acids to alpha,beta-unsaturated carbonyls (Hayashi-Miyaura reaction) (5-0.1 mol % catalyst, up to 95% ee). The iridium complex (S,S)-[Ir((Ph)tropp(Ph))(2)]OTf ((S,S)-6; OTf=SO(3)CF(3)) has been used as a catalyst in the hydrogenation of various nonfunctionalized and functionalized olefins (turnover frequencies (TOFs) of up to 4000 h(-1)) and moderate enantiomeric excesses have been achieved (up to 67% ee). [Ir((Ph)tropp(Ph))(2)]OTf reversibly takes up three equivalents of H(2). The highly reactive octahedral [Ir(H)(2)(OTf)(CH(2)Cl(2))(H(2)-(Ph)tropp(Ph))(2)] could be isolated and contains two hydrogenated monodentate H(2)-(Ph)tropp(Ph) phosphanes, one CH(2)Cl(2) molecule, one triflate anion, and two hydrides. Based on this structure and extensive NMR spectroscopic studies, a mechanism for the hydrogenation reactions is proposed.     

Rapid spectrophotometric determination of chromium(III)

A spectrophotometric procedure is suggested for the determination of Cr(III). The reaction between Cr(III) and 2-(5-bromo-2-pyridylazo)-5-dimethylaminophenol is accelerated by sodium dodecyl sulphate(SDS), sodium benzoate causes a further increase in the absorbance of the chelate. The optimum pH range for the reaction is 5-5.8(benzoate buffer). The chelate exhibits maximum absorbance at 590 nm, obeys Beer's law over the concentration range 0.02-0.56 microg/ml of Cr(III), has molar absorptivity of 7.8 x 10(4) 1. mol(-1) cm(-1) and a Sandell sensitivity of 0.66 ng/cm. The metal to ligand ratio is 1:2 in the absence of SDS and 1:1 in its presence. A procedure for the determination of Cr(III) and Cr(VI), when present together, is described. The method has been applied to the analysis of Cr(III) in tap water.     

1,2-Bis(diphenylphosphino)carborane as a dual mode ligand for both the Sonogashira coupling and hydride-transfer steps in palladium-catalyzed one-pot synthesis of allenes from aryl iodides

[reaction: see text] One-pot allene synthesis from aryl iodides 1 and propargyldicyclohexylamine 2 proceeded in the presence of Pd(2)(dba)(3).CHCl(3) catalyst (2.5 mol %), 1,2-bis(diphenylphosphino)carborane 5 (10 mol %), CuI (15 mol %), and Et(3)N (150 mol %) to give the corresponding allenes 4 in good to high yields. Electron-deficient bidentate phosphines, such as 1,2-bis(diphenylphosphino)carborane 5 and (C(6)F(5))(2)PC(2)H(4)P(C(6)F(5))(2), play the role of a dual mode ligand for both the Sonogashira coupling and hydride-transfer reactions.     

Catalytic, highly enantio- and diastereoselective pinacol coupling reaction with a new tethered bis(8-quinolinolato) ligand

A new class of chiral ligand, tethered bis(8-quinolinol) (TBOxH), is developed. Its chromium complex, TBOxCrCl (3 mol %), effectively catalyzes the pinacol coupling reaction of aromatic aldehydes at room temperature with high yield (up to 94%), high diastereoselectivity (up to dl:meso = 98:2), and high enantioselectivity (up to 98%). The scope of the present method turns out not to be limited to aromatic aldehyde derivatives, as cyclohexanecarboxaldehyde undergoes pinacolization as well (44% yield, dl:meso = 93:7, 84% ee). The method provides an efficient access to enantioenriched 1,2-diols.     

Highly efficient and enantioselective cyclization of aromatic imines via directed C-H bond activation

The first highly enantioselective catalytic reaction involving aromatic C-H bond activation is communicated. Enantioselective cyclization of aromatic ketimines containing alkenyl groups tethered at the meta position of an imine directing group has been achieved using 5 mol % [RhCl(coe)2]2 and 15 mol % of an (S)-binol-derived phosphoramidite ligand. Selectivities of up to 96% ee and up to quantitative yields were obtained. Moreover, the identified catalyst system enables the intramolecular alkylation reaction to be performed at temperatures 75 degrees C lower than our previously reported achiral system. The reaction can even be performed at room temperature for one of the optimal substrates.     

Synthesis and Crystal Structure of Mo(CO)_4(NNP) (NNP=2-(N-Cyclohexyl-N-diphenylphosphinomethyl)aminopyridine)

1 INTRODUCTION The pyridyl-phosphine ligands have been widely used for many years to synthesize hetero- or homo-nuclear metal complexes[1], as electronic differentiation associated with the hard (N) and soft (P) donor atoms dictates their unique reactivities and coordination modes. One of the most common pyridylphosphines studied to date is (2-C5H4N)PPh2 which displays numerous ligating modes ranging from P-coordination and P,N-chelation to the more common P,N-bridging of two metal …     

Efficient aziridination of olefins catalyzed by mixed-valent dirhodium(II,III) caprolactamate

[reaction: see text] A mild, efficient, and selective aziridination of olefins catalyzed by dirhodium(II) caprolactamate [Rh(2)(cap)(4).2CH(3)CN] is described. Use of p-toluenesulfonamide (TsNH(2)), N-bromosuccinimide (NBS), and potassium carbonate readily affords aziridines in isolated yields of up to 95% under extremely mild conditions with as little as 0.01 mol % Rh(2)(cap)(4). Aziridine formation occurs through Rh(2)(5+)-catalyzed aminobromination and subsequent base-induced ring closure. An X-ray crystal structure of a Rh(2)(5+) halide complex, formed from the reaction between Rh(2)(cap)(4) and N-chlorosuccinimide, has been obtained.     

Functionalization of vinylic addition polynorbornenes via efficient copolymerization of norbornene using Ni(II)‐Me complexes

The facile and efficient functionalization of polynorbornene has been achieved through direct copolymerization of norbornene (NB) with 5‐norbornene‐2‐yl acetate (NBA) or 5‐norbornene‐2‐methanol (NBM) using a series of β‐ketiminato Ni(II)‐Me pyridine complexes 1–4 (Scheme 2 ) in the presence of B(C₆F₅)₃. Remarkably, the monomer conversion could reach up to about 96% in 10 min in the NB/NBA copolymerization. The copolymers with wide NBA contents (3.3–38.4 mol %) were obtained by variation of reaction conditions. These copolymers have high molecular weights (MWs) (M_n = 41.8–144 kg/mol) and narrow MW distributions (M_w/M_n = 1.80–2.27). In the absence of alkyl aluminum compounds, a monomer conversion of 81% was observed in the NB/NBM copolymerization, and copolymers with NBM content in the range of 11.2–21.8 mol % were obtained by variation of reaction conditions. In addition, Ni(II)‐Me pyridine complexes 2 was very active at a low B/Ni molar ratio of 6, while bis‐ligand complex 6 bearing the same ligand just showed moderate efficiency at a high B/Ni molar ratio of 20. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Direct catalytic asymmetric aldol reaction of hydroxyketones: asymmetric Zn catalysis with a Et(2)Zn/linked-BINOL complex

Full details of our newly developed catalyses with asymmetric zinc complexes as mimics of class II zinc-containing aldolase are described. A Et(2)Zn/(S,S)-linked-BINOL complex was developed and successfully applied to direct catalytic asymmetric aldol reactions of hydroxyketones. A Et(2)Zn/(S,S)-linked-BINOL 1 = 2/1 system was initially developed, which efficiently promoted the direct aldol reaction of 2-hydroxy-2'-methoxyacetophenone (7d). Using 1 mol % of (S,S)-linked-BINOL 1 and 2 mol % of Et(2)Zn, we obtained 1,2-dihydroxyketones syn-selectively in high yield (up to 95%), good diastereomeric ratio (up to 97/3), and excellent enantiomeric excess (up to 99%). Mechanistic investigation of Et(2)Zn/(S,S)-linked-BINOL 1, including X-ray analysis, NMR analysis, cold spray ionization mass spectrometry (CSI-MS) analysis, and kinetic studies, provided new insight into the active oligomeric Zn/(S,S)-linked-BINOL 1/ketone 7d active species. On the basis of mechanistic investigations, a modified second generation Et(2)Zn/(S,S)-linked-BINOL 1 = 4/1 with molecular sieves 3A (MS 3A) system was developed as a much more effective catalyst system for the direct aldol reaction. As little as 0.1 mol % of (S,S)-linked-BINOL 1 and 0.4 mol % of Et(2)Zn promoted the direct aldol reaction smoothly, using only 1.1 equiv of 7d as a donor (substrate/ligand = 1000). This is the most efficient, in terms of catalyst loading, asymmetric catalyst for the direct catalytic asymmetric aldol reaction. Moreover, the Et(2)Zn/(S,S)-linked-BINOL 1 = 4/1 system was effective in the direct catalytic asymmetric aldol reaction of 2-hydroxy-2'-methoxypropiophenone (12), which afforded a chiral tetrasubstituted carbon center (tert-alcohol) in good yield (up to 97%) and ee (up to 97%), albeit in modest syn-selectivity. Newly developed (S,S)-sulfur-linked-BINOL 2 was also effective in the direct aldol reaction of 12. The Et(2)Zn/(S,S)-sulfur-linked-BINOL 2 = 4/1 system gave aldol adducts anti-selectively in good ee (up to 93%). Transformations of the aldol adducts into synthetically versatile intermediates were also described.     

A new strategy for designing non-C2-symmetric monometallic bifunctional catalysts and their application in enantioselective cyanation of aldehydes

A monometallic bifunctional catalyst, in which only one imidazolyl moiety is directly attached at the 3-position of a binaphthol moiety, has been developed. The ligand (R)-1, which lacks C2-symmetry and flexible linkers, in combination with Ti(OiPr)4, has been demonstrated to promote the enantioselective cyanation of aldehydes with trimethylsilylcyanide (TMSCN), giving excellent enantioselectivities of up to 98 % ee and high yields of up to 99 %. The use of this bifunctional catalytic system obviates the need for additives and is extremely simple as the reagents are added in one portion at the beginning of the reaction. The protocol has been found to tolerate a relatively wide range of aldehydes when 10 mol % of the (R)-1/Ti(OiPr)4 complex is deployed in CH2Cl2 at -40 degrees C, the conditions which proved most practical and effective. The asymmetric cyanations also proceeded with lower catalyst loadings (5 mol %, or even 2 mol %), still giving satisfactory enantiomeric excesses and yields. Interestingly, the use of freshly distilled TMSCN dried over CaH2 gave a low enantioselectivity and only a moderate yield of the adduct as compared with direct use of the commercial reagent. The results of 13C NMR spectroscopic studies implicate HCN as the actual reactive nucleophile.     

Palladium-catalyzed cyclization reactions of 2-vinylthiiranes with heterocumulenes. Regioselective and enantioselective formation of thiazolidine, oxathiolane, and dithiolane derivatives

The first palladium-catalyzed ring-expansion reaction of 2-vinylthiiranes with heterocumulenes to form sulfur-containing five-membered-ring heterocycles is described. This regioselective reaction requires 5 mol % of Pd(2)(dba)(3).CHCl(3) and 10 mol % of bidendate phosphine ligand (dppp, BINAP), at 50-80 degrees C, in THF. The reaction of 2-vinylthiiranes with carbodiimides, isocyanates, and ketenimines affords 1,3-thiazolidine derivatives, whereas the reaction with diphenylketene or isothiocyanates results in the formation of 1,3-oxathiolane or 1,3-dithiolane compounds in good to excellent isolated yields and in up to 78% ee.     

Ag(2)(C(33)H(26)N(2)O(2))(H(2)O)(2)(SO(3)CF(3))(2)].0.5C(6)H(6): a luminescent supramolecular silver(I) complex based on metal-carbon and metal-heteroatom interactions

A novel fulvene-type bidentate ligand 1 has been synthesized by an aroylation reaction of cyclohexyl-substituted cyclopentadienyl anions. Compound 1 crystallizes in the triclinic space group P(-)1, with a = 7.0419(5) A, b = 11.9360(8) A, c = 15.6470(11) A, alpha = 85.1440(10) degrees, beta = 78.1140(10) degrees, gamma = 74.5360(10) degrees, V = 1239.76(15) A(3), and Z = 2. The coordination chemistry of 1 was investigated, and a novel Ag-containing coordination polymer (2), linked by both Ag-heteroatom and Ag-carbon interactions, has been synthesized. The coordination polymer has been fully characterized by infrared spectroscopy, elemental analysis, and single-crystal X-ray diffraction. Compound 2 crystallizes in the triclinic space group P(-)1, with a = 7.1654(5) A, b = 15.7277(11) A, c = 18.8157(13) A, alpha = 73.5150(10) degrees, beta = 89.0410(10) degrees, gamma = 89.0970(10) degrees, V = 1355.19(14) A(3), and Z = 2. The solid-state structure of 2 features a one-dimensional double-chain motif. These double chains are in turn cross-linked to each other via strong interchain O-H...O hydrogen bonds, forming a novel two-dimensional network with remarkably large cavities (effective cross section of ca. 21 x 15 A) that are occupied by benzene guest molecules. Both compounds 1 and 2 are luminescent in the solid state, and a large blue-shift in the emission between the free ligand 1 and the ligand incorporated into complex 2 is observed.     

Copper(II) complexes of acid amide derivatives of 2-aminopyridineand an exogenous ligand

The bidentate ligands, 2-[(N-acetyl)aminopyridine] (AAPH, A) and 2-[(N-benzoyl)aminopyridine] (BAPH, B) have been used to synthesize copper(II) complexes including an exogenous ligand X (X = AcO^–, HCO₂ ^–, N₃ ^– and benzimidazole). The complexes were characterized by elemental analysis, electronic and vibrational spectroscopy, magnetic and e.s.r. studies. E.s.r. parameters and visible spectra indicated that all the complexes are monomers and exist in distorted octahedral geometry except for benzimidazole. With benzimidazole as an exogenous ligand, a five coordinate complex is formed.     

Highly enantioselective Henry (nitroaldol) reaction of aldehydes and alpha-ketoesters catalyzed by N,N'-dioxide-copper(I) complexes

A new chiral N,N'-dioxide-Cu(I) catalyst has been developed for the asymmetric Henry (nitroaldol) reaction. The approach benefited from the easy modification of the chiral space. As the highly effective N-oxide ligand, 1d has been adopted for the Henry reaction with both aromatic and heteroaromatic aldehydes. The corresponding nitro-alcohol products were obtained in good yields with high enantiomeric excesses up to 98%. Moreover, alpha-ketoesters were also catalyzed by this catalyst to give attractive optically active alpha-hydroxy beta-nitro esters containing chiral quaternary carbon centers (up to 99% ee). On the basis of a combination of several techniques including the 1H NMR, ESI-HRMS, and MM2 calculations, the proposed mechanism was presented to explain the origin of reactivity and asymmetric inductivity.     

Highly Enantioselective Transfer Hydrogenation of Ketones with Chiral (NH)2P2 Macrocyclic Iron(II) Complexes

Bis(isonitrile) iron(II) complexes bearing a C₂‐symmetric diamino (NH)₂P₂ macrocyclic ligand efficiently catalyze the hydrogenation of polar bonds of a broad scope of substrates (ketones, enones, and imines) in high yield (up to 99.5 %), excellent enantioselectivity (up to 99 % ee), and with low catalyst loading (generally 0.1 mol %). The catalyst can be easily tuned by modifying the substituents of the isonitrile ligand.     

Dynamical intramolecular metal-to-metal ligand exchange of phosphine and thioether ligands in derivatives PtRu5(CO)16(mu6-C)

The complexes PtRu(5)(CO)(15)(PMe(2)Ph)(mu(6)-C) (2), PtRu(5)(CO)(14)(PMe(2)Ph)(2)(mu(6)-C) (3), PtRu(5)(CO)(15)(PMe(3))(mu(6)-C) (4), PtRu(5)(CO)(14)(PMe(3))(2)(mu(6)-C) (5), and PtRu(5)(CO)(15)(Me(2)S)(mu(6)-C) (6) were obtained from the reactions of PtRu(5)(CO)(16)(mu(6)-C) (1) with the appropriate ligand. As determined by NMR spectroscopy, all the new complexes exist in solution as a mixture of isomers. Compounds 2, 3, and 6 were characterized crystallographically. In all three compounds, the six metal atoms are arranged in an octahedral geometry, with a carbido carbon atom in the center. The PMe(2)Ph and Me(2)S ligands are coordinated to the Pt atom in 2 and 6, respectively. In 3, the two PMe(2)Ph ligands are coordinated to Ru atoms. In solution, all the new compounds undergo dynamical intramolecular isomerization by shifting the PMe(2)Ph or Me(2)S ligand back and forth between the Pt and Ru atoms. For compound 2, DeltaH++ = 15.1(3) kcal/mol, DeltaS++ = -7.7(9) cal/(mol.K), and DeltaG(298) = 17.4(6) kcal/mol for the transformation of the major isomer to the minor isomer; for compound 4, DeltaH++ = 14.0(1) kcal/mol, DeltaS++ = -10.7(4) cal/(mol.K), and DeltaG(298) = 17.2(2) kcal/mol for the transformation of the major isomer to the minor isomer; for compound 6, DeltaH++ = 18(1) kcal/mol, DeltaS++ = 21(5) cal/(mol.K) and DeltaG(298) = 12(2) kcal/mol. The shifts of the Me(2)S ligand in 6 are significantly more facile than the shifts for the phosphine ligand in compounds 2-5. This is attributed to a more stable ligand-bridged intermediate for the isomerizations of 6 than that for compounds 2-5. The intermediate for the isomerization of 6 involves a bridging Me(2)S ligand that can use two lone pairs of electrons for coordination to the metal atoms, whereas a tertiary phosphine ligand can use only one lone pair of electrons for bridging coordination.