Long range heteronuclear COSY

Kozmiriski and Nanz" reported the development of the HECADE experiment that allowed the determination of heteronuclear coupling constants from E-COSY-type crosspeaks. A sensitivity improved HSQC-HECADE pulse sequence has since been developed by the same authors." The HSQC-based GSQMBC experiment reported in 1997 by Sklenaf and coworkers,and discussed in Section 3.3.3, has also been used for the measurement of small, long-range heteronuclear coupling constants. 

Two-dimensional C//correlations such as C//COSY or HC HMQC and HSQC provide the Jqh connectivities, and thereby apply only to those C atoms which are linked to H and not to non-protonated C atoms. Modifications of these techniques, also applicable to quaternary C atoms, are those which are adjusted to the smaller Jqh and Jqh couplings (2-25 Hz, Tables 2.8 and 2.9) Experiments that probe these couplings include the CH COLOC (correlation via long range couplings) with carbon-13 detection (Fig. 2.16) and HC HMBC (heteronuclear multiple bond coherence) with the much more sensitive proton detection (Fig. 2.17)... 

In homonudear shift-correlation experiments like COSY we were concerned with the correlation of chemical shifts between nuclei of the same nuclear species, e.g., H with H. In heteronuclear shift-correlation experiments, however, the chemical shifts of nuclei belonging to different nuclear species are determined (e.g., H with C). These may be one-bond chemical shift correlations, e.g., between directly bound H and C nuclei, or they may be long-range chemical shift correlations, in which the interactions... 

The H-NMR and C-NMR chemical shifts have been assigned and substractures have been deduced on the basis of COSY-45° (Problem 5.13) and other spectroscopic observations. Interpret the HMBC spectrum and identify the heteronuclear long-range coupling interactions between the H and C nuclei. 

Fig. 1. Pulse sequences modified for multiple selective excitation. I ID TOCSY, II het-eronuclear ID NOE, III ID INADEQUATE, IVa heteronuclear ID COSY (optimized to detect Jch), IVb heteronuclear ID COSY (optimized to detect "Jch), V 2D TOCSY-COSY, Via 2D HMBC (designed to detect heteronuclear long-range couplings "Jch only), VIh 2D HMBC (extended pulse sequence to detect both heteronuclear long-range "Jch and...

This is the simple heteronuclear -X COSY (or HETCOR) pulse sequence adapted to long-range correlations simply by adjustment of the Ai and A2 delays. Small coupling constants rule out the use of broad-band proton decoupling during evolution time t by BIRD, and thus the correlation cross-peaks display the structure of proton multiplets, which reduces further the sensitivity of the experiment. 

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