Issue in Honor of Prof. Pierre Vogel ARKIVOC 2014 (iii) 143-153
The bicyclic scaffold of carbapenams has an “open-book” geometry21 that requires that the H-5 proton, the unshared free electron pair from the nitrogen atom and one of the C-2 substituents are on the convex-side (Figure 2, blue color). The other C-2 substituent is on the concave-side (red color) and is subject to a deshielding contribution to its chemical shift by the magnetically anisotropic carbonyl group. Thus, depending on the spatial arrangement of substituents at the C-2 carbon atom in relation to the free electron pair and the .-lactam carbonyl group, their chemical shifts fall in two ranges of about either 3.3-3.7 ppm or 4.0-4.4 ppm (Figure 2). Thus, knowing the absolute configuration at C-2 carbon atom, the absolute configuration at the bridgehead carbon atom C-5 can be easily assigned. Generally, protons having higher chemical shifts are in the plane of carbonyl group and therefore deshielded, thus their germinal partners are located cis to the nitrogen lone pair and to the H-5 proton (Figure 2).
Figure 2. The overview of a geometry of carbapenams.
In 1957 McConnell quantitatively calculated the anisotropy effect of functional groups to explain the respective shielding or deshielding of protons spatially close to the corresponding functional groups.22 It should be noted that the McConnell’s equation and the resulting “anisotropy cones” predict only the anisotropic effect and are not appropriate for the prediction of the net through-space shielding experienced by a proximal nucleus. This limitation is due to the fact that the overall shielding also includes other factors such as orbital interactions and bond polarization.23
It is also evident that for other azabicyclic compounds prepared by us and depicted below, the carbonyl group plays a decisive role in the deshielding effect and the range of changes of chemical shifts caused by the introduction of the carbonyl group (Figure 3).24
Figure 3. The influence of anisotropy of carbonyl function on the 1H NMR chemical shifts for selected azabicycloalkans.
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