Conversion of Allylic Alcohols into Allylic Nitromethyl Compounds via a Palladium-Catalyzed Solvolysis: An Enantioselective Synthesis of an Advanced Carbocyclic Nucleoside Precursor(1)

A two-step reaction sequence to homoallylic nitro compounds from allylic alcohols is presented. Ethoxy carbonylation of the alcohols with ethyl chloroformate provides the corresponding allylic ethyl carbonates in high yields. Exposure of these substrates to catalytic palladium(0) in CH(3)NO(2) initiates a reaction sequence, ionization-decarboxylation-nitromethylation, that culminates with the formation of nitroalkenes. The regio- and stereochemical outcomes of the nitromethyl allylation reaction can be explained by the behavior of the transient pi-allylpalladium complexes. This methodology serves as a centerpiece for the synthesis of an important carbocyclic nucleoside intermediate.     

Surface tension of quantum fluids from molecular simulations

We present the first molecular simulations of the vapor-liquid surface tension of quantum liquids. The path integral formalism of Feynman was used to account for the quantum mechanical behavior of both the liquid and the vapor. A replica-data parallel algorithm was implemented to achieve good parallel performance of the simulation code on at least 32 processors. We have computed the surface tension and the vapor-liquid phase diagram of pure hydrogen over the temperature range 18-30 K and pure deuterium from 19 to 34 K. The simulation results for surface tension and vapor-liquid orthobaric densities are in very good agreement with experimental data. We have computed the interfacial properties of hydrogen-deuterium mixtures over the entire concentration range at 20.4 and 24 K. The calculated equilibrium compositions of the mixtures are in excellent agreement with experimental data. The computed mixture surface tension shows negative deviations from ideal solution behavior, in agreement with experimental data and predictions from Prigogine's theory. The magnitude of the deviations at 20.4 K are substantially larger from simulations and from theory than from experiments. We conclude that the experimentally measured mixture surface tension values are systematically too high. Analysis of the concentration profiles in the interfacial region shows that the nonideal behavior can be described entirely by segregation of H(2) to the interface, indicating that H(2) acts as a surfactant in H(2)-D(2) mixtures.     

DABCO-directed self-assembly of bisporphyrins (DABCO=1,4-diazabicyclo[2.2.2]octane)

Three isomeric zinc bisporphyrins have been prepared by covalently linking together two aminoporphyrins with an isophthalic acid derivative. The porphyrins differ in the substitution pattern on the meso phenyl groups, that is, ortho, meta, or para. Titrations carried out by UV-visible and 1H NMR spectroscopy have been used to map out the stabilities and the stoichiometries of the complexes formed with 1,4-diazabicyclo[2.2.2]octane (DABCO) in chloroform. The ortho- and meta-substituted bisporphyrins form 1:1 intramolecular sandwich complexes. The para-substituted bisporphyrin cannot adopt the cofacial conformation required for this type of complex and forms a higher order 2:2 intermolecular assembly, which is stable over a wide range of DABCO concentrations.     

Minimization of water vapor interference in the analysis of non-methane volatile organic compounds by solid adsorbent sampling

Water vapor can be a significant interference in the analysis of air for non-methane volatile organic compounds (NMVOCs) using solid-adsorbent sampling techniques. The adsorbent materials used in sampling cartridges have different hydrophobic characteristics, and it is therefore necessary to characterize solid-adsorbent cartridges over a wide range of humidity. Controlled humidity experiments were performed to assess the extent of water vapor interference when samples are collected onto AirToxics solid-adsorbent cartridges. It was found that elevating the temperature of the cartridge to 10 degrees C above the temperature of the air sample greatly reduced water vapor adsorption and interferences and resulted in > or = 90% recovery of NMVOCs, biogenic VOCs and chlorofluorocarbons. Similar collection efficiencies were obtained at ambient temperature by reducing the relative humidity to > or = 60% in the sample by dilution with dry, scrubbed ambient air. A procedure also was developed and optimized for dry-purging cartridges prior to analysis. However, under optimized conditions, significant losses of C3-C5 compounds still occurred under highly humid conditions. It was determined that these losses were due to reduced retention during sampling rather than loss during the dry purge procedure. The dry purge method was shown to be adequate at high humidities for sampling NMVOCs with retention indices greater than 500.     

Rotavap simulation and the estimation of boiling points

A Java applet that predicts solute losses during evaporation from a binary or ternary mixture has been developed which gives good agreement with experiment and can be used to estimate the boiling points of solutes, making use of information which is often collected and then discarded (http://www.ch.cam.ac.uk/magnus/rotavap/).     

The crystal structure of 1,1-bis(η5-cyclopentadienyl)-2,3,4,5-tetraphenylzirconole

The crystal and molecular structure of (η⁵-C₅H₅)₂Zr[C₄(C₆H₅)₄] has been determined by single crystal X-ray diffraction methods. The compound is isostructural with its titanium and hafnium analogues, and crystallizes in the monoclinic space group P2₁/n with unit cell parameters a = 13.790(5), b = 11.136(5), c = 18.692(7) », β = 92.82(4)°, and ?_calc = 1.34 g cm^?3 for Z = 4. Full-matrix least-squares refinement converged with a conventional R value of 0.049 for 2986 observed reflections. The metallocyclic ring is planar to within 0.05 », and the π-electron density is largely localized. The two independent ZrC(σ) bond lengths are 2.250(5) and 2.265(6) ». The ZrC(η⁵) distances range from 2.482(6) to 2.546(7) », and average 2.521(20) ». A comparison of zirconium- and hafnium-carbon bonds based on the data available shows that for M = Hf the MC bonds are shorter for all cases: C(sp), C(sp²), C(sp³), C(η⁵).     

Chiroptical properties of 2-substituted pyrrolidines

The CD spectra of L-2-methylpyrrolidine, L-prolinol, and their N-methylated derivatives have been determined. As in the 2-substituted piperidines, N-methylation results in an inversion of the sign of the Cotton effects (CE). However, the sign of the long-wavelength CE does not follow the simple helicity rule found for 2-substituted piperidines, since the pyrrolidine ring is itself chiral and makes its own contributions to the observed CE's. The rotational contribution due to pyrrolidine ring chirality appears to be opposite in sign to and larger in magnitude than that due to the 2-substituent in both the secondary and the tertiary amines.     

The synthesis and properties of certain N-methylated 5-diazouracils

The reduction of 1-methyl-, 3-methyl- and 1,3-dimethyl-5-nitrouracil (Ia-c) to the corresponding 5-aminouracils (IIa-c) is described. Diazotization of 5-amino-1-methyluracil (IIa) and 5-amino-1,3-dimethyluracil (IIc) gave 5-diazouracils which were characterized as thermally stable C6 covalent hydrates (III and XIII). Diazotization of 5-amino-3-methyluracil (IIb) gave anhydro 5-diazo-3-methyluracil (X) which underwent covalent methanolation and thermally reversible covalent hydration. Treatment of III and XIII with hot methanol resulted in solvent exchange of the C6 hydroxyl groups by a mechanism which may involve initial formation of diazoethers. Treatment of the methanolates (IV, XI and XIV) with dimethylamine resulted in coupling at the diazo group with a concomitant expulsion of the C6 methoxyl groups to give 5-(3,3-dimethyl-1-triazeno)uracils (XVa-c).     

Crystal supramolecular motifs: columns of embracing Ph3PMe+ or Ph3PCI+ cations controlling formation of

The crystal structures of (Ph3PCl)2[Cu3Cl8] (1) (triclinic, space group P1, a = 9.480(6) A, b = 10.243(8) A, c = 11.232(6) A, alpha = 86.76(4) degrees, beta = 66.62(5) degrees, gamma = 83.92(4) degrees, Z = 1) and (Ph3PMe)2[Cu3Br8] (2) (triclinic, space group P1, a = 9.795(4) A, b = 10.472(4) A, c = 11.392(4) A, alpha = 86.67(3) degrees, beta = 66.67(3)degrees, gamma = 83.14(3) degrees, Z = 1), reported here, demonstrate a new supramolecular motif for cations of the type Ph3PY+ where Y is CH3 or Cl. The crystals contain columns of cations propagated by alternating 6-fold phenyl embraces (6PE) and pseudo-6PE: the pseudo-6PE described here contains four phenyl rings and two hetero groups (Cl or CH3), and is symbolized as 4P2Y. The zigzag sequence of cations engaged in ...6P...4P2Y...6P...4P2Y... is similar to the zigzag chain of infinite 6-fold phenyl embraces (ZZI6PE) frequently adopted by Ph4P+ cations in crystals. One-dimensionally nonmolecular anion chains with repeat unit [Cu3X8] run parallel to and between the columns of cations. The coordination geometry in the [Cu3X8(2-)]1 to infinity chain has not been observed in crystals with other cations, and it is postulated that the attractive interactions between cations in the pseudo-ZZI6PE crystal supramolecular motif control the geometry of the anions through the requirement for commensurability of cation columns and anion chains.     

Ordering the reductive and cytochrome P450 oxidative steps in demethylsterigmatocystin formation yields general insights into the biosynthesis of aflatoxin and related fungal metabolites

The biosynthesis of the potent environmental carcinogen aflatoxin B1 involves ca. 15 steps beyond the first polyketide intermediate. Central among these is the rearrangement of the anthraqinone versicolorin A to the xanthone demethylsterigmatocystin. Genetic evidence strongly suggests that two enzymes are required for this process, a cytochrome P450, AflN, and a probable NADPH-dependent oxidoreductase, AflM. Given the overall redox change evident in this skeletal rearrangement, two rounds of oxidation and a reduction necessarily occur. Earlier experiments indicated that reductive deoxygenation of versicolorin A is not the first step. In the present report we consider a mechanistic alternative that AflM-mediated reduction is instead the last of these three reactions prior to formation of the xanthone intermediate. To this end, 9-hydroxydihydrodemethylsterigmatocystin was prepared by total synthesis as was its 9-deoxy analogue, an established aflatoxin precursor. During the final isolation of the "angular" synthetic xanthone targets it was found that acid catalysis promoted their isomerization to thermodynamically favored "linear" xanthones. Whole-cell and ground-cell incubations of the 9-hydroxy- and 9-deoxyxanthones were conducted with a mutant strain of Aspergillus parasiticus blocked at the first step of the pathway and examined for their ability to support aflatoxin production. The 9-deoxyxanthone gave dramatically enhanced levels of the mycotoxin. The 9-hydroxyxanthone, on the other hand, afforded no detectable increase in aflatoxins above controls, indicating that reductive deoxygenation at C-9 of a xanthone precursor does not take place in aflatoxin biosynthesis. Constraints imposed by earlier studies and the experiments in this paper serve to eliminate simple and intuitive conversions of versicolorin A to demethylsterigmatocystin and lead inescapably to a more subtle reaction sequence of oxidation-reduction-oxidation. Previous puzzling observations of extensive A-ring hydrogen exchange in the course of the rearrangement of versicolorin A to demethylsterigmatocystin have now been explained by a new mechanism that is consistent with all extant data. We propose that P450-mediated aryl epoxidation (AflN) initially disrupts the aromatic A-ring of versicolorin A. Oxirane opening enables A-ring proton exchange, as does the subsequent AflM-mediated reductive step. A second cycle of P450 oxidation (AflN), this time a Baeyer-Villiger cleavage, enables decarboxylation and the formation of demethylsterigmatocystin. Mechanistic and stereoelectronic principles that underlie this proposal are described and may prove general as illustrated in biogenetic hypotheses for four other fungal anthraquinone --> xanthone transformations.