Caryophyllene Oxide HMBC

One way to keep track of these data is to construct a table listing the carbon resonances in one direction and the proton resonances in the other. In Table 5.1, the carbons are given across the top and protons along the side. The numbering for caryophyllene oxide is the same in Table 5.1 as in all the figures. 

There are two protons on C-2, which are labeled H-2 and H-2 these protons have different chemical shifts, yet we expect them to act much the same way in the HMBC. Thus, we have a useful independent check of our HMBC assignments for each pair of diastereotopic protons in caryophyllene oxide. For H-2 at 1.45 ppm, we have the same five correlations that we have for H-2 at 1.63 ppm. As we study the spectrum and the table more closely, we find that we have exquisitely detailed structural information that can be deciphered with a methodical approach. 

An important point about quaternary carbons requires comment. Until now, we have had no direct correlations for carbons without protons, nor have we been able to see through heteroatoms such as oxygen, nitrogen, sulfur, etc. Both the two- and three-bond coupling correlations of HMBC provide us with both types of critical information. For example, C-4 of caryophyllene oxide at 59.1 ppm has no attached protons, and so far it has only appeared in the l3C spectrum of the compound, and we know that it is quaternary 

During th the frequencies that evolve are not the chemical shifts of the coupled nuclei as they are in a typical DQF-COSY. Instead, it is the sum of their offsets 

FIGURE 5.19 The INADEQUATE spectrum of caryophyllene oxide. Correlation lines are drawn as an aid. 

---

The HMBC for caryophyllene oxide (Figure 5.18) allows us to completely confirm the structure of caryophyllene oxide by giving us the required indirect carbon-carbon connectivities. An analysis of the structure of caryophyllene oxide reveals that there should be 87 cross peaks this number is derived from considering each of the 15 carbon atoms and counting the number of chemical-shift-distinct protons at the a-positions and the number of chemical-shift-distinct protons at the /3-positions. In order to keep track of all of those interactions, one must be methodical indeed. 

The common theme so far in our correlation experiments has been to allow spins to evolve during q under the influence of directly coupled nuclear spins. We have seen the power of COSY, HMQC, HMBC, and INADEQUATE to provide us with detailed structural information for ipsenol, caryophyllene oxide, and lactose. In this section, we will develop another method for showing correlations and apply it to molecules with distinct, isolated proton spin systems such as carbohydrates, peptides, and nucleic acids. 

Before we tackle the HMBC for caryophyllene oxide, let us practice on ipsenol. The HMBC for ipsenol (Figure 6.19) looks like the HETCOR (with its axes switched) for ipsenol with two obvious differences There are considerably more correlations and the one-bond correlations (HMQC) are gone. Interpretation of HMBCs requires a degree of flexibility because we do not always find what we expect to find. In particular, whereas two-bond correlations (2/CH) are almost always found, the three-bond (3/CH) correlations are occasionally absent. The variations in correlations that we find result from the variations in the magnitude of 2Jni and VC coupling constants. 

The HMBC for caryophyllene oxide (Figure 6.20) allows us to completely confirm the structure of caryophyllene oxide by giving us the required indirect carbon-carbon connectivities. An analysis of the structure of caryophyllene oxide reveals that there should be 87... 

FIGURE 6.20. (a) The 300-MHz (F2) HMBC spectrum of caryophyllene oxide, and (b) an expanded view showing greater digital resolution. 

---