Uncovering Key Structural Features of an Enantioselective Peptide-Catalyzed Acylation Utilizing Advanced NMR Techniques.

We report on a detailed NMR spectroscopic study of the catalyst-substrate interaction of a highly enantioselective oligopeptide catalyst that is used for the kinetic resolution of trans-cycloalkane-1,2-diols via monoacylation. The extraordinary selectivity has been rationalized by molecular dynamics as well as density functional theory (DFT) computations. Herein we describe the conformational analysis of the organocatalyst studied by a combination of nuclear Overhauser effect (NOE) and residual dipolar coupling (RDC)-based methods that resulted in an ensemble of four final conformers. To corroborate the proposed mechanism, we also investigated the catalyst in mixtures with both trans-cyclohexane-1,2-diol enantiomers separately, using advanced NMR methods such as T1 relaxation time and diffusion-ordered spectroscopy (DOSY) measurements to probe molecular aggregation. We determined intramolecular distance changes within the catalyst after diol addition from quantitative NOE data. Finally, we developed a pure shift EASY ROESY experiment using PSYCHE homodecoupling to directly observe intermolecular NOE contacts between the trans-1,2-diol and the cyclohexyl moiety of the catalyst hidden by spectral overlap in conventional spectra. All experimental NMR data support the results proposed by earlier computations including the proposed key role of dispersion interaction.

Exploration of the Photodegradation of Naphtho[2,3-g] quinoxalines and Pyrazino[2,3-b]phenazines.

Nitrogen-containing polycyclic aromatic hydrocarbons are very attractive compounds for organic electronics applications. Their low-lying LUMO energies points towards a potential use as n-type semiconductors. Furthermore, they are expected to be more stable under ambient conditions, which is very important for the formation of semiconducting films, where materials with high purity are needed. In this study, the syntheses of naphtho[2,3-g]quinoxalines and pyrazino[2,3-b]phenazines is presented by using reaction conditions, that provide the desired products in high yields, high purity and without time-consuming purification steps. The HOMO and LUMO energies of the compounds are investigated by cyclic voltammetry and UV/Vis spectroscopy and their dependency on the nitrogen content and the terminal substituents are examined. The photostability and the degradation pathways of the naphtho[2,3-g]quinoxalines and pyrazino[2,3-b]phenazines are explored by NMR spectroscopy of irradiated samples affirming the large influence of the nitrogen atoms in the acene core on the degradation process during the irradiation. Finally, by identifying the degradations products of 2,3-dimethylnaphtho[2,3-g]quinoxaline it is possible to track down the most reactive position in the compound and, by blocking this position with nitrogen, to strongly increase the photostability.

Conformational analysis of small organic molecules using NOE and RDC data: A discussion of strychnine and α-methylene-γ-butyrolactone.

To understand the properties and/or reactivity of an organic molecule, an understanding of its three-dimensional structure is necessary. Simultaneous determination of configuration and conformation often poses a daunting challenge. Thus, the more information accessible for a given molecule, the better. Additionally to (3)J-couplings, two sources of information, quantitative NOE and more recently also RDCs, are used for conformational analysis by NMR spectroscopy. In this paper, we compare these sources of conformational information in two molecules: the configurationally well-characterized strychnine 1, and the only recently configurationally and conformationally characterized α-methylene-γ-butyrolactone 2. We discuss possible sources of error in the measurement and analysis process, and how to exclude them. By this means, we are able to bolster the previously proposed flexibility for these two molecules.

Exploring the conformational space of bridge-substituted dithienylcyclopentenes.

Stimuli responsive compounds and materials are of high interest in synthetic chemistry and materials science, with light being the most intriguing stimulus due to the possibility to remote control the physicochemical properties of a molecule or a material. There is a constant quest to design photoswitches with improved switching efficiency and especially diarylethene-type switches promise photo cyclization quantum yields up to unity. However, only limited attention has been paid towards the influence of the solution conformation on the switching efficiency. Here, we describe a detailed NMR spectroscopic investigation on the conformational distribution of bridge-substituted dithienylcyclopentenes in solution. We could discriminate between several photoactive and photoinactive as well as two diastereomorphous conformations and show that the trends observed in the switching efficiency match the conformer populations obtained from state of the art NMR parameters in solution.

Accurate determination of one-bond heteronuclear coupling constants with "pure shift" broadband proton-decoupled CLIP/CLAP-HSQC experiments.

We report broadband proton-decoupled CLIP/CLAP-HSQC experiments for the accurate determination of one-bond heteronuclear couplings and, by extension, for the reliable measurement of small residual dipolar coupling constants. The combination of an isotope-selective BIRD((d)) filter module with a non-selective (1)H inversion pulse is employed to refocus proton-proton coupling evolution prior to the acquisition of brief chunks of free induction decay that are subsequently assembled to reconstruct the fully-decoupled signal evolution. As a result, the cross-peaks obtained are split only by the heteronuclear one-bond coupling along the F2 dimension, allowing coupling constants to be extracted by measuring simple frequency differences between singlet maxima. The proton decoupling scheme presented has also been utilized in standard HSQC experiments, resulting in a fully-decoupled pure shift correlation map with significantly improved resolution.

The influence of electronic modifications on rotational barriers of bis-NHC-complexes as observed by dynamic NMR spectroscopy.

There has been much debate about the σ-donor and π-acceptor properties of N-heterocyclic carbenes (NHCs). While a lot of synthetic modifications have been performed with the goal of optimizing properties of the catalyst to tune reactivity in various transformations (e.g. metathesis), direct methods to characterize σ-donor and π-acceptor properties are still few. We believe that dynamic NMR spectroscopy can improve understanding of this aspect. Thus, we investigated the intramolecular dynamics of metathesis precatalysts bearing two NHCs. We chose four systems with one identical NHC ligand (N,N'-Bis(2,4,6-trimethylphenyl)-imidazolinylidene (SIMes) in all four cases) and NHC(ewg) ligands bearing four different electron-withdrawing groups (ewg). Both rotational barriers of the respective Ru-NHC-bonds change significantly when the electron density of one of the NHCs (NHC(ewg)) is modified. Although it is certainly not possible to fully dissect σ-donor and π-acceptor portions of the bonding situations in the respective Ru-NHC-bond via dynamic NMR spectroscopy, our studies nevertheless show that the analysis of the rotation around the Ru-SIMes-bond can be used as a spectroscopic parameter complementary to cyclic voltammetry. Surprisingly, we observed that the rotation around the Ru-NHC(ewg)-bond shows the same trend as the initiation rate of a ring-closing metathesis of the four investigated bis-NHC-complexes.