Regio- and enantioselective allylic amination of achiral allylic esters catalyzed by an iridium-phosphoramidite complex

A new catalytic asymmetric process, the iridium-catalyzed enantioselective allylic amination of (E)-cinnamyl and terminal aliphatic allylic carbonates, was developed by exploring complexes of chiral phosphoramidites. The reaction provided branched secondary and tertiary allylic amines in high yields with excellent regio- and enantioselectivity (13 examples over 94% ee). Although the reactions in polar solvent such as DMF, EtOH, and MeOH were fast, they gave low enantiomeric excesses. In contrast, reactions in THF displayed the most suitable balance of rate and enantioselectivity. Both the binaphthol unit and the disubstituted amine in the phosphoramidite affected reactivity and selectivity, and complexes of O,O'-(R)-(1,1'-dinaphthyl-2,2'-diyl)-N,N'-di-(R,R)-1-phenylethylphosphoramidite provided the highest reactivity and selectivity. Primary and cyclic secondary amines reacted at room temperature, and acyclic diethylamine reacted at 50 degrees C. p-Methoxy-substituted cinnamyl carbonate reacted similarly to the unsubstituted cinnamyl carbonate, but the o-methoxy-substituted substrate gave lower enantiomeric excess. High ee's were also observed for the products from the reaction of furanyl- and alkyl-substituted (E)-allylic carbonates.     

ULTRASTRUCTURAL STUDIES ON THE MECHANISM OF THE PHOTODYNAMIC THERAPY OF TUMORS

Abstract Balb/c mice bearing a transplanted MS-2 fibrosarcoma were injected with 2.5 mg kg ¹ of either tetra(4-sulfonatophenyl/porphine (TPPS) in phosphate-buffered saline or 0.5 mg kg⁻¹ of Zn²⁺-phthalocyanine (Zn-Pc) incorporated into unilamellar liposomes of dipalmitoyl-phosphatidylcholine. Chromatographic studies showed that TPPS is mainly transported in the serum by globulins and albumin, while Zn-Pc is specifically bound by lipoproteins. Exposure of the injected mice to red light (300 J cm⁻²) caused extensive tumor necrosis. The ultrastructural analysis of tumor specimens taken from mice at 15 h after PDT showed that TPPS photoinduces a preferential necrosis of the neoplastic cells, while Zn-Pc causes severe photodamage to both the vascular system and the neoplastic cells. The different modes of tumor photosensitization by TPPS and Zn-Pc are discussed on the basis of the transport mechanism of the two dyes.     

Ruthenium-catalyzed anti-Markovnikov hydroamination of vinylarenes

A ruthenium-catalyzed intermolecular, anti-Markovnikov hydroamination of vinylarenes with secondary aliphatic and benzylic amines is reported. The combination of Ru(cod)(2-methylallyl)2, 1,5-bis(diphenylphosphino)pentane, and triflic acid was the most effective catalyst of those tested. Control reactions conducted without ligand or acid did not form the amine. The reaction of morpholine, piperidine, 4-phenylpiperazine, 4-BOC-piperazine, 4-piperidone ethylene ketal, and tetrahydroisoquinoline with styrene in the presence of 5 mol % of this catalyst formed the corresponding beta-phenethylamine products in 64-96% yield, with 99% regioselectivity, and without enamine side products. Acyclic amines such as n-hexylmethylamine and N-benzylmethylamine reacted with styrene in 63 and 50% yields, respectively. Alkyl-, methoxy-, and trifluoromethyl-substituted styrenes reacted with morpholine in the presence of this catalyst or a related one containing 1,1'-bis(diisopropylphosphino)ferrocene as ligand to give the products in 51-91%. Further, the hydroamination of alpha-methyl styrene was observed for the first time with a homogeneous transition metal catalyst. Preliminary mechanistic studies showed that the reaction occurred by direct, irreversible, anti-Markovnikov hydroamination and that the mechanism of the ruthenium-catalyzed hydroamination is likely to be distinct from that of the recently reported rhodium-catalyzed reaction.     

The effects of cationic and zwitterionic micelles on the keto-enol interconversion of 2-phenylacetylfuran and 2-phenylacetylthiophene

The presence of micelles from cationic and zwitterionic surfactants increases the apparent acidity of either the keto and the enol forms of 2-phenylacetylfuran (2PAF) and 2-phenylacetylthiophene (2PAT). This effect can be attributed to the affinity of the surfactant micelles for the enolate of the two substrates. Although the equilibrium constants for keto-enol tautomerism of 2PAF and 2PAT, K_T=[enol]/[ketone]=pK_a^KH−pK_a^EH, do not change much, the presence of micelles provides an efficient method for producing appreciable quantities of the enolates under mild experimental conditions and in aqueous solutions. The obtained rate-profiles for the ketonisation reactions and the consistency of the kinetic rate constants over a wide range of ‘pH’ in several overlapping buffers indicate that the pH of the aqueous pseudophase (but not that at the micellar surface) can be controlled by buffers. Moreover, the increase of the acidity and the decrease of the ‘water’ rate of ketonisation of the enols of 2PAF and 2PAT upon addition of surfactants allow the uncovery of a metal ion catalysed pathway that cannot be observed in absence of surfactants.     

Iridium-catalyzed regio- and enantioselective allylation of ketone enolates

The regio- and enantioselective alpha-allylation of unstabilized ketone enolates with unsymmetrical allylic carbonates to form the branched substitution products in the presence of metallacyclic iridium catalysts is reported. The products, branched gamma,delta-unsaturated ketones, were obtained from readily available silyl enol ethers and achiral Boc-protected allylic alcohols in high regioselectivities and enantioselectivities (91-96% ee). The combination of CsF and ZnF2 was shown to promote this reaction and suppress the formation of diallylation byproducts. In addition, iridium complexes derived from simple phosphoramidite ligands were shown to catalyze this reaction with excellent selectivities, and spectroscopic data show that a cyclometalated Ir precatalyst is formed in situ. This process provides an enantioselective access to synthetically important bifunctional compounds, which are generally accessible, but in racemic form, through Claisen rearrangements. Ten examples of the reactions of aromatic, as well as aliphatic, substrates are reported.     

Thermodynamic properties of the ternary system MTBE+1-propanol+hexane

Experimental excess molar enthalpies and excess molar volumes of the ternary system x₁MTBE+x₂1-propanol+(1-x₁-x₂) hexane and the involved binary mixtures have been determined at 298.15 K and atmospheric pressure. Excess molar enthalpies were measured using a standard Calvet microcalorimeter, and excess molar volumes were determined from the densities of the pure liquids and mixtures, using a DMA 4500 Anton Paar densimeter. The UNIFAC group contribution model (in the versions of Larsen et al., and Gmehling et al.) has been employed to estimate excess enthalpies values. Several empirical expressions for estimating ternary properties from experimental binary results were applied.     

Regio- and enantioselective iridium-catalyzed intermolecular allylic etherification of achiral allylic carbonates with phenoxides

An enantioselective and regioselective iridium-catalyzed allylic etherification is described. The reaction of sodium and lithium aryloxides with achiral (E)-cinnamyl and terminal aliphatic allylic electrophiles in the presence of 2 mol % of an iridium-phosphoramidite complex provides chiral allylic aryl ethers in high yields and excellent levels of regio- and enantioselectivity. Lithium aryloxides containing a single substituent at an ortho, meta, or para position as well as sterically hindered phenoxides were tolerated. Reactions in THF displayed the most suitable balance of rate, regio-, and enantioselectivity. High ee's were also observed for the products from the reaction of alkyl (E)-allylic carbonates.     

Long-term diffusive samplers for the indoor air quality evaluation

Three kinds of diffusion samplers, conceived to perform long-term samplings in indoor sites are illustrated in this work. Two of them, in part deriving from the previous "Analyst for VOC" device, extend the field of application up to the semi-volatile organic compounds (SVOC), PAHs and nicotine in particular. A third device, which employs a basic barium hydroxide solution as an absorbing medium, is proposed for the determination of carbon dioxide levels which indicate the air change quality in the indoor sites. Laboratory and field experiments, performed in order to assess the reliability of the proposed devices, are shown. A monthly monitoring campaign, performed at three private apartments in Rome and its outskirts highlights that the indoor pollution levels are a complex function of various concurrent and opposite factors, like external air pollution, internal sources, air change rate and sink effect of surfaces, which contribute to depletion phenomena through adsorption and/or decomposition processes.     

On the cycle index of point groups

In this brief work we express the cycle index of the molecular point groups as a function of a limited number of initial geometrical parameters. Such parameters are the number of elements composing the domain D of sites of substitutions in the molecule belonging to the point group G, and the numbers of sites of D lying on the symmetry elements for G.     

Resolution of benzo[a]pyrene in complex mixtures of other polycyclic aromatic hydrocarbons. Comparison of two spectrofluorimetric methods applied to water samples

Two spectrofluorimetric methods, second-derivative constant-energy synchronous luminescence (SDCESL) and constant-wavelength synchronous luminescence (CWSL) in combination with multiple linear regression (MLR), for the quantification of benzo[a]pyrene (BaP) at sub-ng mL-1 levels, in the presence of benzo[b]fluoranthene (BbFt), benzo[k]fluoranthene (BkFt), benzo[ghi]perylene (BghiP) and indeno[1,2,3-cd]pyrene (IP), were developed and compared in detail. SDCESL presents lower limits of detection and quantification than CWSL/MLR and also gives more exact and precise results for levels close to the quantification limit. For BaP, SDCESL achieved quantification limits of 0.019 ng mL-1 in river waters and 0.007 ng mL-1 in drinking waters. This work offers a sensitive, precise, accurate, rapid, simple and economic methodology for monitoring BaP in waters for public consumption, meeting all the requirements of the EC Directive 98/83/CE that fixes the maximum admissible limit for this polycyclic aromatic hydrocarbon in drinking waters at of 0.010 ng mL-1.