The investigation of reaction mechanisms is a complex task that usually requires the use of several techniques. To obtain as much information as possible on the reaction and any intermediates – possibly invisible to one technique – the combination of techniques is a solution. In this work we present a new setup for combined UV/Vis and NMR spectroscopy and compare it to an established alternative. The presented approach allows a versatile usage of different commercially‐available components like mirrors and fiber bundles as well as different fixed pathlengths according to double transmission or single transmission measurements. While a previous approach is based on a dip‐probe setup for conventional NMR probes, the new one is based on a micro‐Helmholtz coil array (LiquidVoxel™). This makes the use of rectangular cuvettes possible, which ensure well‐defined pathlengths allowing for quantification of species. Additionally, very low quantities of compound can be analyzed due to the microfabrication and small cuvette size used. As proof‐of‐principle this new setup for combined UV/Vis and NMR spectroscopy is used to examine a well‐studied photochromic system of the dithienylethene compound class. A thorough comparison of the pros and cons of the two setups for combined UV/Vis and NMR measurements is performed.

Until now, the intermediate responsible for the acyl transfer of a highly enantioselective tetrapeptide organocatalyst for the kinetic resolution of trans-cycloalkane-1,2-diols has never been directly observed. It was proposed computationally that a π-methylhistidine moiety is acylated as an intermediate step in the catalytic cycle. In this study we set out to investigate whether we can detect and characterize this key intermediate using NMR-spectroscopy and mass spectrometry. Different mass spectrometric experiments using a nano-ElectroSpray Ionization (ESI) source and tandem MS-techniques allowed the identification of tetrapeptide acylium ions using different acylation reagents. The complexes of trans-cyclohexane-1,2-diols with the tetrapeptide were also detected. Additionally, we were able to detect acylated tetrapeptides in solution using NMR-spectroscopy and monitor the acetylation reaction of a trans-cyclohexane-1,2-diol. These findings are important steps towards the understanding of this highly enantioselective organocatalyst.

The kinetic resolution of trans-cyclohexane-1,2-diol with a lipophilic oligopeptide catalyst shows extraordinary selectivities. To improve our understanding of the factors governing selectivity, we quantified the Gibbs energies of interactions of the peptide with both enantiomers of trans-cyclohexane-1,2-diol using nuclear magnetic resonance (NMR) spectroscopy. For this we use advanced methods such as transverse relaxation (R2), diffusion measurements, saturation transfer difference (STD), and chemical shift (δ) analysis of peptide-diol mixtures upon varying their composition (NMR titrations). The methods employed give comparable and consistent results: The molecular recognition by the catalyst is approx. 3 kJmol−1 in favor of the preferentially acetylated (R,R)-enantiomer in the temperature range studied. Interestingly, the difference of 3 kJ mol−1 is also confirmed by results from reaction monitoring of the acylation step under catalytic conditions, indicating that this finding is true regardless of whether the investigation is performed on the acetylated species or on the free catalyst. To arrive at these conclusions the self-association of both catalyst and substrate in toluene were found to play an important role and thus need to be taken into account in reaction screening.