Absolute configuration determination
Chiroptical Inversion for Isolated Vibronic Transitions of Supersonic Beam-Cooled Molecules. Circular dichroism-resonance-enhanced multiphoton ionization (CD-REMPI) was used for CD measurements on several single vibronic transitions of supersonic beam-cooled (R)-(+)-1-phenylethanol. Due to the low molecular densities within a supersonic beam and the expected small anisotropy factor of 1-phenylethanol in the permille region, the precision of the experimental method had to be significantly improved. Therefore, a single laser pulse evaluation combined with a twin-peak technique enabled within the used supersonic beam setup is presented. For the electronic transition S0 → S1 of (R)-(+)-1-phenylethanol (π → π* transition of the phenyl ring at 266 nm) ten different vibrational modes as well as the 000-transition were investigated with one-color (1 + 1) CD-REMPI. The results deliver new experimental insights on the influence of molecular vibrations on the anisotropy factor. TD-DFT theoretical predictions show how the angle between the electronic and magnetic transition dipole moments of the electronic transition can be modified by different vibrational modes, making even a flip of the sign of the anisotropy factor possible.
This minireview is addressed to readers with a background in basic organic chemistry and spectroscopy, but without a specific knowledge of NMR, ECD, VCD and ORD. Herein we summarize the role of quantum mechanical ab initio prediction of spectral properties in NMR and chiroptical spectroscopies. Illustrative examples of the application of prediction of chemical shifts and scalar couplings to the determination of chemical constitution and relative configurations of natural products are presented. Once the relative configuration is determined, the absolute configuration can be established with the help of ECD, VCD and ORD spectroscopies assisted by quantum mechanical prediction of the corresponding spectra. The scope, limitations and advantages of these chiroptical spectroscopies are presented, in order to help the reader in choosing a suitable combination of ab initio and spectroscopic tools when cing a particular problem.
Both enantiomers of an optically active trialkynyl(phenyl)methane (the key building blocks in the construction of a stable expanded cubane) have been prepared. The strategy involved the resolution of a racemic intermediate by means of HPLC on a chiral stationary phase. The absolute configuration of this intermediate was unambiguously assigned by using vibrational circular dichroism (VCD) and optical rotatory dispersion (ORD), in combination with density functional theory (DFT) calculations.
A thiazolopyrimidine derivative resulting from high-throughput screening was found to be active toward 2-methylerythritol 2,4-cyclodiphosphate synthase (IspF) from Mycobacterium tuberculosis and Plasmodium falciparum , with respective IC 50 values of 6.1±0.8 and 9.6±1.5 µ M . Some of the prepared derivatives exhibit weak in vitro activity against the protozoan parasite P. falciparum.
Triple Bingel addition of enantiomerically pure cyclotriveratrylene-tethered trimalonates to C60 was reinvestigated with regard to the regio- and diastereoselectivity. Electronic and vibrational circular dichroism studies showed that the addition proceeds regioselectively, yielding trans -3, trans -3, trans -3 tris-adducts, contrary to earlier reports.
Conformational assignment: The mechanism of chiral induction in an optically pure 1,3-diethynylallene, from the central chiral allene moiety into directly adjacent TCBD chromophores, was confirmed and clarified. Only one low-energy conformer is found in calculations of the potential energy surface, which closely resembles the X-ray crystal structure. Simulations of the CD spectrum by time-dependent DFT showed a total agreement (see picture), in terms of position and sign, for all Cotton effects when compared to the experimental spectrum.