Methylene group, diastereotopicity

The diastereomers 251/ewf-251 and 252/ent-252 could be separated and were decom-plexed separately. From the fraction of 251/ewt-251,253 was obtained with 85% ee (e.r. = 92.5 7.5), and the fraction of 252/ent-252 yielded ewt-253 with 88% ee (e.r. = 6 94). A similar situation results from the reaction with tributyltin chloride or alkylation reagents, but the diastereomeric ratio is strongly dependent on the electrophile. The following conclusion is drawn from these and further experiments The enantiomeric ratio is determined by a selection of the chiral base between the diastereotopic methylene groups, since the benzylic carbanionic centres are labile, whereas the diastereomeric ratio results from the relative rate of the electrophile approach syn or anti with respect to the A-methyl group. One question remains—why are opposite d.r. values formed in the alkylation by methyl iodide and ethyl iodide ... 

The benzyl methylene groups in 115 are diastereotopic (J = 13.5 Hz) restricted rotation of the dimethylamino group is apparent in 111. ... 

By contrast to its spiro sulfurane analog. 31 in a CDCI, and nitrobenzene solution at room temperature displays a rapid polytopal rearrangement that results in the averaging of the diastereotopic protons of the methylene groups. The increase in the frequency of the polytopal rearrangements on going from sulfuranes to telluranes is in accord with theoretical predictions (77ZOB2011). 

The biosynthesis of the p-lactam antibiotic penicillin (Fig. 65), and also of cephalosporin, involves incorporation of L-valine and the question arises as to which of the two diastereotopic terminal methyl groups of the valine occupies which position in the penicillin. (In the case of cephalosporin, the question is as to which methyl group is incorporated into the six-membered ring and which becomes the methylene group of the carbinyl acetate.) The problem has been solved by two groups 65d,141) by synthesis of specifically 13C methyl labeled valine (cf. Fig. 42, and p. 35) which was then biosynthetically incorporated in the antibiotics. The position of the 13C in the resulting antibiotic molecules was determined by 13C NMR spectroscopy. 

Note that the chiral center accounts for the fact that the protons of each of the two aliphatic methylene groups are also diastereotopic. As a result, the rather simple structure presents a challenge in assigning the spectrum to the given structure. 

We will reserve further discussion of diastereotopic methylene groups until the next section on H — UC COSY or HMQC. 

There are only three cases possible for each carbon atom. If a line drawn encounters no cross peaks, then the carbon has no attached hydrogens. If the drawn line encounters only one cross peak, then the carbon may have either 1,2, or 3 protons attached if 2 protons are attached, then they are either chemical shift equivalent or they fortuitously overlap. If the horizontal line encounters two cross peaks, then we have the special case of diastereotopic protons attached to a methylene group. Much of this information will already be available to us from DEPT spectra (see Section 4.6) indeed, the HMQC spectrum should, whenever possible, be considered along with the DEPT. 

We can begin with either a carbon or a proton resonance and obtain equivalent results. We will use the carbon axis as our starting point because we usually have less overlap there. For example, a line drawn parallel to the proton axis at about 68 ppm on the carbon axis (the carbinol carbon) intersects five cross peaks none of the five correlations corresponds to the attached proton (VCH) at 3.8 ppm. Four of the cross peaks correspond to the two pairs of diastereotopic methylene groups (2.48, 2.22,1.45, and 1.28 ppm) and these represent, 2iCH, or two-bond couplings. The fifth interaction (3/CH) correlates this carbon atom (68 ppm) to the isopropyl methine proton (1.82 ppm), which is bonded to a carbon atom in the /3-position. The other carbon atom in a /3-position has no attached protons so we do not have a correlation to it from the carbinol carbon atom. Thus, we have indirect carbon connectivities to two a-carbons and to one of two /3-carbons. 

Another useful example can be found by drawing a line from the carbon resonance at 41 ppm. This carbon is the C-5 methylene and we first note that correlations to the attached protons at 2.48 and 2.22 ppm are absent. There is only one a-carbon that has one or more attached protons its corresponding correlation is found to the C-4 carbinol methine proton at 3.83 ppm. There are three /3-carbons and they all have attached protons. The C-3 methylene carbon shows indirect correlation through both of its diastereotopic protons at 1.45 and 1.28 ppm. The C-7 olefinic methine proton gives a cross peak at 6.39 ppm as do the protons of the olefinic methylene group attached to C-6 at 5.16 and... 

The exocyclic olefinic methylene protons show obvious COSY correlations to one another. In addition, we note weak cross peaks between the olefinic protons at 4.86 and 4.97 ppm and an apparent diastereotopic methylene group (2.11 and 2.37 ppm) and a quartet at 2.60 ppm, respectively. These interactions are reminiscent of the long-range allylic coupling that we saw in ipsenol we could assign these correlations to the diastereotopic methylene C-7 and the methine at C-9. For now, we will be cautious and conservative, and return to this point later in the chapter. 

The presence of an asymmetric carbon atom adjacent to the CH2C1 group gives rise to the different chemical environments of these diastereotopic protons. When a molecule contains an asymmetric carbon atom, the protons on any methylene group are usually diastereotopic. They may or may not be resolved in the NMR, however, depending on the differences in their environments. 

H, /-modulated and Si NMR spectra of compound 26 were reported <2003JOM73>. Its structure was proved by the signals of the diastereotopic protons of all three methylene groups and two signals of diastereotopic Me groups in the H NMR spectrum. 

---