Molecular dynamics simulations with an all-atom model were carried out to study the ionic liquid 1-n-butyl-3-methylimidazolium hexafluorophosphate, [bmim][PF(6)]. Analysis was carried out to characterize a number of structural and dynamic properties. It is found that the hydrogen bonds are weaker than expected, as indicated by their short lifetimes, which is due to the fast rotational motion of anions. Transport properties such as ion diffusion coefficients and ionic conductivity were also measured on the basis of long trajectories, and good agreement was obtained with experimental results. The phenomenon that electrical conductivity of ionic liquids deviates from the Nernst-Einstein relation was well reproduced in our work. On the basis of our analysis, we suggest that this deviation results from the correlated motion of cations and anions over time scales up to nanoseconds. In contrast, we find no evidence for long-lived ion-pairs migrating together.

Mandelalide A and three congeners had recently been isolated as the supposedly highly cytotoxic principles of an ascidian collected off the South African coastline. Since these compounds are hardly available from the natural source, a concise synthesis route was developed, targeting structure 1 as the purported representation of mandelalide A. The sequence involves an iridium-catalyzed two-directional Krische allylation and a cobalt-catalyzed carbonylative epoxide opening as entry points for the preparation of the major building blocks. The final stages feature the first implementation of terminal acetylene metathesis into natural product total synthesis, which is remarkable in that this class of substrates had been beyond the reach of alkyne metathesis for decades. Synthetic 1, however, proved not to be identical with the natural product. In an attempt to clarify this issue, NMR spectra were simulated for 20 conceivable diastereomers by using DFT followed by DP4 analysis; however, this did not provide a reliable assignment either. The puzzle was ultimately solved by the preparation of three diastereomers, of which compound 6 proved identical with mandelalide A in all analytical and spectroscopic regards. As the entire "northern sector" about the tetrahydrofuran ring in 6 shows the opposite configuration of what had originally been assigned, it is highly likely that the stereostructures of the sister compounds mandelalides B-D must be corrected analogously; we propose that these natural products are accurately represented by structures 68-70. In an attempt to prove this reassignment, an entry into mandelalides C and D was sought by subjecting an advanced intermediate of the synthesis of 6 to a largely unprecedented intramolecular Morita-Baylis-Hillman reaction, which furnished the γ-lactone derivative 74 as a mixture of diastereomers. Whereas (24R)-74 was amenable to a hydroxyl-directed dihydroxylation by using OsO4 /TMEDA as the reagent, the sister compound (24S)-74 did not follow a directed path but simply obeyed Kishi's rule; only this unexpected escape precluded the preparation of mandelalides C and D by this route. A combined spectroscopic and computational (DFT) study showed that the reasons for this strikingly different behavior of the two diastereomers of 74 are rooted in their conformational peculiarities. This aspect apart, our results show that the OsO4 /TMEDA complex reacts preferentially with electron deficient double bonds even if other alkenes are present that are more electron rich and less encumbered. Finally, in a brief biological survey authentic mandelalide A (6) was found to exhibit appreciable cytotoxicity only against one out of three tested human cancer cell lines and all synthetic congeners were hardly active. No significant fungicidal properties were observed.

The surface tension γ of the room temperature ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate, [bmim][PF 6 ] in short, has been evaluated in the framework of Guggenheim's corresponding-states analysis using experimental data taken from the literature as well as new simulation data. The critical temperature is estimated to be T c ) 1100 K ( 100 K from the surface-tension data, which are analyzed in terms of the empirical expressions of Guggenheim and of Eo ¨tvo ¨s. Adopting this value of T c , a critical density of F c ) 0.35 g cm -3 ( 0.04 g cm -3 is obtained from the experimental coexistence curve using the linear-diameter rule. The estimates of F c obtained from our simulation data are lower by 13-25%. According to Guggenheim, the reduced surface tension), where M r denotes the molar mass and c a constant, is supposed to be a universal function of the reduced temperature T/T c for all pure fluids. While many nonpolar, weakly polar, and moderately polar liquids adhere to this principle of corresponding states, deviations from Guggenheim's master curve are seen for strongly polar, hydrogen-bonding substances and for simple inorganic molten salts, such as NaCl and KCl. We find that, despite its ionicity, the data for [bmim][PF 6 ], both from experiment and from simulation, follow the master curve for at most moderately polar liquids, thereby indicating significant differences from the physicochemical properties of simple inorganic molten salts.