Observation of potentially troublesome (2) JCC correlations in 1,1-ADEQUATE spectra.

Despite the tremendous usage of HMBC to establish long-range H-1-C-13 and H-1-N-15 heteronuclear correlations, an inherent drawback of the experiment is the indeterminate nature of the (n)J(XH) correlations afforded by the experiment. A priori there is no reliable way of determining whether a given (n)J(CH) correlation is, for example, via two-, three-, or sometimes even four-bonds. This limitation of the HMBC experiment spurred the development of the ADEQUATE family of NMR experiments that rely on, in the case of 1,1-ADEQUATE, an out-and-back transfer of magnetization via the (1)J(CC) homonuclear coupling constant, which is significantly larger than (n)J(CC) (where n=2-4) couplings in most cases. Hence, the 1,1-ADEQUATE experiment has generally been assumed to unequivocally provide the equivalent of (2)J(CH) correlations. The recent development of the 1,1- and 1,n-HD-ADEQUATE experiments that can provide homodecoupling for certain (1)J(CC) and (n)J(CC) correlations has increased the sensitivity of the ADEQUATE experiments significantly and can allow acquisition of these data in a fraction of the time required for the original iterations of this pulse sequence. With these gains in sensitivity, however, there occasionally come unanticipated consequences. We have observed that the collapse of proton multiplets, in addition to providing better s/n for the desired (1)J(CC) correlations can facilitate the observation of typically weaker (2)J(CC) correlations across intervening carbonyl resonances in 1,1-HD-ADEQUATE spectra. Several examples are shown, with the results supported by the measurement of the (2)J(CC) coupling constants in question using J-modulated-HD-ADEQUATE and DFT calculations. Copyright (c) 2016 John Wiley & Sons, Ltd.