Anomalous Nuclear Overhauser Effects in Carbon‐Substituted Aziridines: Scalar Cross‐Relaxation of the First Kind

Abstract

Anomalous NOESY cross-peaks that cannot be explained by dipolar cross-relaxation or chemical exchange are described for carbon-substituted aziridines. The origin of these is identified as scalar cross-relaxation of the first kind, as demonstrated by a complete theoretical description of this relaxation process and by computational simulation of the NOESY spectra. It is shown that this process relies on the stochastic modulation of J-coupling by conformational transitions, which in the case of aziridines arise from inversion at the nitrogen center. The observation of scalar cross-relaxation between protons does not appear to have been previously reported for NOESY spectra. Conventional analysis would have assigned the cross-peaks as being indicative of a chemical exchange process occurring between correlated spins, were it not for the fact that the pairs of nuclei displaying them cannot undergo such exchange.Among the powerful NMR structure and conformation elucidation techniques, [1] nuclear Overhauser effect (NOE) experiments play a central role because they map the spatial proximity of neighboring spins.[2] The experimental techniques used to observe magnetization transport due to NOEs (NOE spectroscopy or NOESY) can also reveal the presence of chemical exchange processes, for which the methods are also known as exchange spectroscopy (EXSY).For small molecules (M r < ca. 1000 Da) in non-viscous liquids at ambient temperatures, 1 H-1 H cross-peaks are negative (opposite sign to the diagonal-peaks) for the NOE and positive (same sign as the diagonal-peaks) for pairs of signals undergoing chemical exchange. For large molecules (M r > ca. 2000 Da), aggregates or with viscous solvents, the sign of the 1 H-1 H Overhauser effect undergoes a welldocumented inversion and cross-peaks become positive, appearing similar to those arising from chemical exchange processes.The theory of spin relaxation processes in general [3] and of NOEs in particular [2] is one of the most developed areas of magnetic resonance spectroscopy, meaning deviations from the behaviors described above are rare indeed. Herein, we report anomalous NOESY observations for a series of Csubstituted NH aziridines 1 a-d, for which the usual interpretations offered no acceptable explanation.During the development of methodology for the synthesis and desulfinylation of N-sulfinyl terminal aziridines by some of the current authors, [4] extensive spectroscopic analysis was carried out to establish the integrity of the aryl-substituted NH aziridines 1 a,b (due to prior literature mischaracterization [5] ).A NOESY spectrum of 2-phenylaziridine (1 a) in dry CD 2 Cl 2 at 298 K exhibited unexpected strong positive crosspeaks between the broad N-H resonance and all three CH protons of the aziridine (Figure 1 a), in addition to the anticipated NOEs producing negative cross-peaks between aziridine CH protons, characteristic of rapidly tumbling molecules. The aziridine CH protons also produced the expected negative cross-peaks with the nearby phenyl protons....

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