A Comprehensive Discussion of HMBC Pulse Sequences: 4. Establishing Two-Bond Correlations from HMBC and Related Experiments

Abstract

The utility of the HMBC experiment for structure elucidation is unquestionable, but the nature of the coupling pathways leading to correlations in an HMBC experiment creates the potential for misinterpretation. This misinterpretation potential is intimately linked to the size of the long-range heteronuclear couplings involved, and may become troublesome in those cases of a particularly strong 2JCH correlation that might be mistaken for a 3JCH correlation or a 4JCH correlation of appreciable strength that could be mistaken for a weaker 3JCH correlation. To address these potential avenues of confusion, work from several laboratories has been focused on the development of what might be considered “coupling pathway edited” long-range heteronuclear correlation experiments that are derived from or related to the HMBC experiment. The first example of an effort to address the problems associated with correlation path length was seen in the heteronucleus-detected XCORFE experiment described by Reynolds and co-workers that predated the development of the HMBC experiment. Proton-detected analogs of the HMBC experiment intended to differentiate 2JCH correlations from nJCH correlations where n = 3, 4, include the 2J,3J-HMBC, HMBC-RELAY, H2BC, edited-HMBC, and HAT H2BC experiments. The principles underlying the critical components of each of these experiments are discussed and experimental verification of the results that can be obtained using model compounds are shown. This contribution concludes with a brief discussion of the 1,1-ADEQUATE experiments that provide an alternative means of identifying adjacent protonated and non-protonated carbon correlations by exploiting 1JCC correlations at natural abundance.