Hydrogen diastereotopic

B The fourth possibility arises in chiral molecules, such as (R)-2-butanol. The two — CH2- hydrogens at C3 are neither homotopic nor enantiotopic. Since replacement of a hydrogen at C3 would form a second chirality center, different diastereomers (Section 9.6) would result depending on whether the pro-R or pro-S hydrogen were replaced. Such hydrogens, whose replacement by X leads to different diastereomers, are said to be diastereotopic. Diastereotopic hydrogens are neither chemically nor electronically equivalent. They are completely different and would likely show different NMR absorptions. 

Another classical case with respect to ort/zo-effects is found for 2-nitrostyrene78. The conceivable regio- and stereo-specifically labelled 2-nitrostyrenes have, in addition to the ring-labelled isotopomer, been studied by collision activation mass spectrometry79. Undoubtedly, the most striking result was the nearly equal contribution of both (in the neutral molecule diastereotopic) hydrogens of the fi-carbon. 

The ease of glycerol, with chirotopic diastereotopic hydrogens in the absence of a stereo-genic unit, requires special treatment. The first descriptor is derived as above, but the second is that of the constitutionally nearest chirotopic atom. 

The 2H-NMR spectra of these derivatized carboxylic acids sometimes are a powerful and simple alternative for the estimation of optical purity. Similar analysis of diastcrcomcric derivatives of a-deuteriated primary alcohols with (5)-2-0-acetylmandelic acid and primary amines with (-)-(1 S, 2/ )-camphanoy 1 chloride is also possible. However, in most cases the shift differences in the simple H-NMR spectra of the same derivatives are large enough to obtain the diastereomeric ratio. Shift differences of the two a-methylenic diastereotopic hydrogens are typically between <5 = 0.05 and 0.2. 

The chemical shift differences of the diastereotopic hydrogens are listed in Table 17 they depend strongly on solvent effects, as expected for an ionic product. They are in the range of 8 = 0.01 -0.1, well suited for measurement of the enantiomeric purity of the phosphanes. An alternative method for the measurement of Horner phosphanes is by 13C-NMR spectroscopy of diastereomeric complexes formed with [>/3-( + )-0 7 ,57 )-pinenyl]nickel bromide dimer73. 

Asymmetric bond disconnection is less frequently employed than asymmetric bond formation for the synthesis of chiral, nonracemic compounds. The substrates for these transformations contain either enantiotopic (diastereotopic) hydrogen atoms or enantiotopic (diastereotopic) functional groups. In some cases the classification of a given transformation of such a substrate as asymmetric bond disconnection or bond formation is somewhat arbitrary. Thus, enantiotopic and diastereotopic group differentiation is also described at appropriate places in various sections but more specifically in part B of this volume. 

Asymmetric Reactions Involving Enantiotopic and Diastereotopic Hydrogen Atoms... 

As for tetrasubstituted double bonds bearing methyl substituents (Scheme 7), migration toward higher alkyl substituents is much faster than toward methyl groups. If the alkyl substituent bears diastereotopic hydrogen atoms migration... 

Therefore, there are five different types of hydrogens in 2-bromobutane. However, the chemical shifts of the diastereotopic hydrogens on C-3 will be very similar. In general, the two hydrogens of a CH2 group are diastereotopic when a chirality center is present. 

Mevalonic acid is indeed the true precursor of the terpenes but it is a C6 compound and so it must lose a carbon atom to give the C5 precursor. The spare carbon atom becomes C02 by an elimination reaction. First, the primary alcohol is pyrophosphorylated with ATP (Chapter 49) then the CO2H group and the tertiary alcohol are lost in a concerted elimination. We know it is concerted because labelling the diastereotopic hydrogen atoms on the CH2CO2H group reveals that the elimination is stereospecific. 

An example of the differentiation of diastereotopic hydrogens occurs in the formation of a /8-lactam, 60, from an optically active A-methylbenzyl-A-chloroacetamide acetonitrile, 59. When the starting chiral compound was (-t-)-R-a-(l-... 

The last stereochemically cryptic feature of this transformation concerns the specificity of the enzyme for the diastereotopic hydrogen atoms at C-l of 1,2-propanediol. To resolve this point Zagalak et al. [18] prepared ( R,2R)- and (1 R,2S)-1,2-[ 1 -2H,]propanediols (12 and 13) by reducing (R) and (5)-lactaldehydes with (4/ )-[4-2H,]NADH and liver alcohol dehydrogenase (Fig. 9). The cyclic acetals of 12 and 13, formed from nitrobenzaldehyde, gave different H-NMR spectra, and their configurations were determined by spectral comparison [20] with racemic reference compounds of known (relative) configuration. 

Fig. 9. Stereospecificity of the dioldehydratase for the diastereotopic hydrogen atoms at C-l in propanediol.

The specificity of the enzyme for the diastereotopic hydrogen atoms at the C-l of glycerol was also determined using (1 / , 2 / )-[ 1 -2 H, ]glycerol as a substrate (see Chapter 3 for the method of preparation). Again, in spite of an isotope effect deuterium migration was observed exclusively to furnish, after chemical oxidation, ( + )-(S)-3-[2-2H,]hydroxypropionic acid (Fig. 13). 

Fig. 24. Specification of the diastereotopic hydrogen atoms in (K)- and (S)methylsuccinic acid.

As in achiral ketone 54, the systems with a chiral auxiliary attached to the C2 carbon should have two conformations in which the carbonyl chromophore is tilted toward one or the other diastereotopic hydrogens at C4 and C. The two lowest energy conformations computed [B3LYP/6-31G(d)] for the menthyl ester of 2-benzoyladamantane-2-carboxylic acid are shown in Fig. 11. Clearly the carbonyl is tilted toward either side, and the two conformers do not have the same energy. As indicated in Fig. 11, the energy difference between the two structures is 2.3 kcal/mol. This small difference allows equilibrium between the two con-formers favoring low de in solution. 

Although the phenylalanine-derived fragment of cytochalasin D (148) possesses the configuration of the L-amino-acid both D- and L-phenylalanine are equally effective precursors. Incorporation occurs with complete loss of tritium and N from C-2 and extensive loss of tritium from both diastereotopic hydrogens at C-3. These losses could be explained as occurring in part during the course of transamination and phenylpyruvic acid may then be implicated. This acid depressed the incorporation of D-phenylalanine as measured relative to the L-isomer (2S)-[4 - H]- and (2/ 5)-[2- C]-phenylalanine were fed the cytochalasin isolated showed an increased H C ratio, cf. discussion on p. 1. It follows that L-phenylalanine rather than the D-isomer is the primary precursor of cytochalasin D (148). 

Figure 1.12 Fischer representation of the diastereotopic hydrogens in D-xylose (right) and N-acetylneuraminic acid (left).

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