A glance into the catalytic pathway from substrate to products offers valuable insight into its reaction mechanism. Unfortunately, the enlightening reaction intermediates are typically short-lived and at low-concentration, so that their characterisation by NMR can be challenging. Several strategies can be adopted to detect these: (1) making use of state-of-the-art instrumentation and/or special experiments which can boost the sensitivity of the NMR detection or (2) using chemical strategies to promote and stabilise intermediates, so that they become long-lived on the NMR timescale. Here are some representative accomplishments:
Detection of gem-hydration carbene intermediate with PHIP: The inherently poor sensitivity of NMR comes from the fact that the signal originates from the thermal polarisation of nuclear spins inside a strong magnetic field. There exist however other possible sources of NMR polarisation. For instance, when molecular hydrogen in its stable para-spin state (para-H2) is transferred pairwise to a molecule, e.g. in the hydrogenation reaction of a triple bond, the symmetry of the molecule is broken while the anti-parallel spin orientation is preserved. In effect, the para-H2 “stores” 100% polarisation which can be “released” via its transfer onto a molecule leading to a theoretical 10000x boost in sensitivity. This method (para-Hydrogen Induced Polarization or PHIP) was used for the study of short-lived and low-concentration reaction intermediates. It has been used in our laboratory in the mechanistic study of Ru-catalysed trans-hydration of alkyne.
Detection of the Terminal Hydride Intermediate in [FeFe] Hydrogenase: Using high-sensitivity solution 1H NMR spectroscopy at room temperature, strongly paramagnetically broadened and shifted 1H signals could be detected and assigned to key hydrogen positions in the iron-rich clusters of the [FeFe] hydrogenase from Chlamydomonas reinhardtii in different states of the hydrogen-producing catalytic cycle. Among these, an intermediate state involving a terminal iron-bound hydride, recognized as crucial for the catalytic mechanism, was directly detected, thus proving its occurrence unequivocally at physiological conditions for the first time.
Stabilization and Structural Study of a Chiral Dirhodium Carbene Intermediate: For over a decade, the remarkable catalytic properties of the bimetallic dirhodium “paddlewheel” complex to activate C-H bond and used in asymmetric cyclopropanation, cycloaddition and ylid formation have been resting on a key Rh-carbene intermediate which was never before detected due to its known instability. In complement to the valuable crystallographic information on stabilized Rh-carbene intermediates, NMR could not only confirm that structural features such as the position and orientation of the carbene ligand are also present in solution but also could deliver a detailed dynamic portrait essential for the understanding of the reaction mechanism.
 D. J. Tindall, C. Werle, R. Goddard, P. Philipps, C. Farès, A. Fürstner, J. Am. Chem. Soc. 2018, 140, 1884-1893.
 C. Sommer, S. Rumpel, S. Roy, C. Farès, V. Artero, M. Fontecave, E. Reijerse, W. Lubitz, J. Biol. Inorg. Chem. 2018, 23, 481-491.
 S. Rumpel, C. Sommer, E. Reijerse, C. Farès, W. Lubitz, J. Am. Chem. Soc. 2018, 140, 3863-3866.
 S. Rumpel, E. Ravera, C. Sommer, E. Reijerse, C. Farès, C. Luchinat, W. Lubitz, J. Am. Chem. Soc. 2018, 140, 131-134.
 A. Guthertz, M. Leutzsch, L. M. Wolf, P. Gupta, S. M. Rummelt, R. Goddard, C. Farès, W. Thiel, A. Fürstner, J. Am. Chem. Soc. 2018, 140, 3156-3169.
 C. Werlé, R. Goddard, P. Philipps, C. Farès, A. Fürstner, Angew. Chem. Int. Ed. 2016, 55, 10760-10765.
 C. Werlé, R. Goddard, P. Philipps, C. Farès, A. Fürstner, J. Am. Chem. Soc. 2016, 138, 3797-3805.
 M. Leutzsch, C. Farès, MPI Kohlenforschung Forschungsbericht 2016 2016. doi:
 M. Leutzsch, L. M. Wolf, P. Gupta, M. Fuchs, W. Thiel, C. Farès, A. Fürstner, Angew. Chem. Int. Ed. 2015, 54, 12431-12436.