Very Long-Range Correlations (ⁿJ_C,H n > 3) in HMBC Spectra

Abstract

The structural elucidation of natural products and complex organic molecules relies heavily on the application of proton detected heteronuclear NMR. Among these techniques, the HMBC NMR experiment remains as the most popular among the methods that sample long range coupling constants. The HMBC (C-H) experiment allows the assignment of structural fragments through correlations between protons and carbons separated by more than one bond, usually two or three (2 JC,H and 3 JC,H). It is also possible to obtain valuable information, sometimes crucial, through very long-range, or nonstandard correlations, n JC,H n>3; they can, surprisingly, appear in standard HMBC spectra, or looked for by performing several HMBC experiments with different long-range delays and using a deeper threshold in the contour plot.

Application of 1,n-ADEQUATE and Modified Variants to Structure Elucidation and Spectral Assignment Problems

“…This two-step approach to spin-spin coupling calculations has shown better accuracy in comparison with that of the unmodified basis sets. 26 As mentioned earlier, it is instructive to consider the range and frequency of 1 J CC coupling constants for strychnine (11) as shown in Figure 4. The distribution of one-bond 13 C-13 C couplings ranges from the smallest at 32 Hz to just slightly less than 72 Hz for the C21-C22 vinyl coupling.…”

“…26 In an analogous manner, the J-modulated ADEQUATE experiment can also be optimized for long-range n J CC couplings. That experiment was also done and the n J CC coupling constants for strychnine (11) large enough to measure successfully are superimposed with the 1 J CC coupling constants in the plot shown in Figure 6. Synthesis of Euglobal-G2.…”

“…The data were acquired at 600 MHz using a 1.7 mm MicroCryoProbe ™ with a 1. was undertaken. Strychnine (11) was used as a model compound for that study. Its broad range of 1 J CC couplings presented a challenge for the uniformity of 1 J CC inversion.…”

“…9 In large part, the difficulty in dealing with proton-deficient structures is based on the necessity of being able to access 4 J CH and longer range 1 H-13 C heteronuclear couplings, which cannot be readily carried out with HMBC data even when optimized for small coupling constants, e.g., 3 Hz. 10,11 The ADEQUATE experiments date back to the work of Griesinger and coworkers in 1996. 12 -15 There were four initial variants of the experiment designated by the prefixes 1,1-, 1,n-, n,1-, and n,n-or m,n-ADEQUATE.…”

“…This observation is graphically illustrated with two segments from the inverted 1 J CC 1,n-ADEQUATE spectra of strychnine (11) shown in Figure 12. The aliphatic portion of the dual optimized spectrum acquired with 1 J CC / n J CC optimizations of 57/9.5 and 64/8 Hz is shown in Figure 12a.…”