Protons enantiotopic

Enantiotopic protons can have different chemical shifts in a chiral solvent Because the customary solvent (CDCI3) used in NMR measurements is achiral this phenomenon is not observed in routine work... 

Replacing one of these protons by chlorine as a test group gives (/ )-2-chloro-l-propanol replacing the other gives (.S)-2-chloro-l-propanol. Enantiotopic protons have the sane chemical shift, regardless of the field strength of the NMR spectrometer. 

In recent years, enantioselective variants of the above transannular C-H insertions have been extensively stiidied. The enantiodetermining step involves discrimination between the enantiotopic protons of a meso-epoxide by a homochiral base, typically an organolithium in combination with a chiral diamine ligand, to generate a chiral nonracemic lithiated epoxide (e.g., 26 Scheme 5.8). Hodgson... 

Enantiotopic proton/group A proton (or group) which if replaced by another hypothetical group (not already found in the molecule), would yield a pair of enantiomers. 

The use of chiral shift reagents, e.g. tris-[3-(trifluoromethyl)- or -(hepta-fluoropropyl)-hydroxymethylene)-d-camphorato)]europium, praseodymium, or ytterbium, in the determination of optical purities of chiral alcohols, ketones, esters, epoxides, amines, or sulphoxides, or in the separation of n.m.r. signals of internally enantiotopic protons e.g. PhCHjOH), has been described. 

The reaction became particularly interesting for synthetic purposes when enantiose-lective variants were elaborated. Thus, the deprotonation of meio-epoxides like 89 converts an achiral compound into a chiral one, the carbenoid 90. If the lithiation has been carried out with a differentiation of the enantiotopic protons, the subsequent transannular... 

The highly selective abstraction of one of the enantiotopic protons in carbamates due to the presence of (—)-sparteine dnring the metalation step, onthned in equation 11, proved itself to be a particularly fruitful concept in the context of chiral economy Thus the protocol permits one to convert a prochiral snbstrate into a non-racemic product in remarkable enantioselectivity. Usually, metalated carbamates like 21 generated by this method react with electrophiles under retention of confignration (eqnation 70). In the metalation step, mediated by (—)-sparteine, the pro-5 proton is removed predominantly, and reaction products 169 are obtained in >95% ee as a rnle (eqnation 70) . ... 

A much more efficient procedure consists in the deprotonation of prochiral substrates 4 by chiral base 5 (equation 2). The removal of the enantiotopic protons in 4 proceeds through diastereotopic transition states having different energies AG and thus yielding the diastereomeric carbanions 6 and epi-6 in unequal amounts (equation 2). 

The asymmetric (—)-sparteine-mediated deprotonation of alkyl carbamates was unprecedented until discovered in 1990 °. For the first time, protected 1-alkanols could be transformed generally to the corresponding carbanionic species by a simple deprotonation protocol. Moreover, an efficient differentiation between enantiotopic protons in the substrate took place and the extent of stereoselection could be stored in a chiral ion pair, bearing the chiral information at the carbanionic centre. 

All evidence points to a kineticaUy controlled differentiation between enantiotopic protons, leading to a configurationally stable intermediate 150 , which is stereospecifically substituted with retention of the configuration. Experiments with the deuteriated substrate 149-D (D for H at N-CH2 in 149) and the results of kinetic smdies support this assumption . The ligand (—)-sparteine (11) in 150 contributes to enhanced configurational stability this can be concluded from the lithiodestannylation experiment shown in equation 34. 

Achiral A,A-diisopropyl-ferrocenecarboxamide (440) was deprotonated by Snieckus and coworkers by n-BuLi/(—)-sparteine (11) (equation 119) . The base discriminates well between the enantiotopic protons H(2) and H(5) in the substituted ring to form the diastereomer 441 with high selectivity. Trapping the intermediate with a couple of different electrophiles afforded the substitution products 442a-d with 85 to 99%... 

As for any desymmetrization of meso compounds, enantioselectivity comes from the ability of a homochiral base to distinguish between two enantiotopic protons, in this particular case, to discriminate between the two pseudo-axial protons of the rapidly equilibrating enantiomeric half-chair conformations 51 and 52 (Scheme 25). 

Figure 10. 250 MIU H-NMR spectra of 2,2,4,4-ietramcthyl-3-pentanol and 4,4-dimethyl-2,2-di(methyl-<7,(pentan-1.1,1 -c/,-3-ol (in chloroform-rfat 24 C) in the presence orEu(hfc)3 (substrate/LSR 1 2)103 a) discrimination of internally enantiotopic protons rendered diastcreotopic in a chiral environment, b) discrimination of externally enantiotopic protons rendered diastereotopic in a chiral environment.

In principle, the enantiotopic protons of bromochloromethane will be anisochronous in a chiral solvent. However, it requires a fair degree of association to make the chemical shift difference visible. This requirement may be satisfied in hydrogen-bonding solvents ... 

But, you will recall that enantiomers are chemically indistinguishable unless they are in a chiral environment. Therefore we expect shifts of enantiotopic hydrogens to be identical, unless they are in a chiral environment. To summarize, enantiotopic protons normally will have the same chemical shifts, whereas diastereotopic protons normally will have different chemical shifts. 

It is of interest that the protons (or fluorine nuclei) in CH2F2 should become anisogamous in a chiral solvent1065, since the enantiotopic protons in CH2CFBr would become diastereotopic in such a solvent however, attempts to demonstrate such anisogamy have not so far been successful106). 

For each compound given below (a-o), describe all spin systems (using Pople notation where appropriate), chemically shift equivalent protons, magnetic equivalent protons, enantiotopic protons, and diastereotopic protons. 

In cases where the deprotonation occurs not at the enantiotopic protons of a methylene group, but at more widely separated enantiotopic positions, configurational stability of the... 

If the imaginary replacement of either of two protons forms enantiomers, then those protons are said to be enantiotopic. The NMR is not a chiral probe, and it cannot distinguish between enantiotopic protons. They are seen to be equivalent by NMR. ... 

Human beings are such a system so are enzymes, and the asymmetric reagents you will meet in Chapter 45. But NMR machines are not. NMR machines cannot distinguish right and left—the NMR spectra of two enantiomers are identical, for example. It is not a matter of enantiomers in the molecule in question—it has a plane of symmetry and is achiral. Nonetheless, the relationship between these two hydrogens is rather like the relationship between enantiomers (the two possible ways of colouring the Hs are enantiomers—mirror images) and so they are called enantiotopic. Enantiotopic protons appear identical in the NMR spectrum. 

In Chapter 32 we showed that homotopic and enantiotopic protons are identical by NMR. Similarly, homotopic faces or groups are always chemically identical. Enantiotopic faces are also chemically identical, provided that all the reagents in the reaction in question are achiral or racemic. In Chapter 45. we will consider what happens to enantiotopic faces when enantiomerica ly pure reagents are used. 

This is again a concerted reaction and again we know that by proton labelling. One of the two enantiotopic protons (Hs in the diagram) is lost from the bottom face of the allylic CH2 group while the new proton is added to the top face of the alkene. This is an anti rearrangement overall. 

In a chiral medium, enantiotopic protons become diastereotopic and thus their 1H-NMR signals are split (see ref. [87]). Therefore, a positive test with the Pirkle s reagent is the necessary but not sufficient condition for chirality... 

A further question concerns the fate of the tritium in the second molecule of (5S)-[5-3H]ALA during the dehydratase reaction. The C-5 atom of the ALA molecules becomes the C-2 atom of PBG and loses one of its enantiotopic protons, while the ring is aromatized. When (5S)-[5-3H]ALA was reacted on the dehydratase and the product was isolated by careful chromatography on cellulose, the resulting PBG retained the tritium also at position 2 [81]. This means that the aromatization of the presumptive intermediate 71 takes place in an enzyme-bound state and involves specific abstraction of the 2-HRe atom (Fig. 39). 

The loss of the symmetry planes intersecting the single phenolic units can be seen also by the signals of enantiotopic protons or groups in the residues Y or R, which become diastereotopic in the dimer (Figure 30). 

Figure 30. Splitting of signals for enantiotopic protons/groups in 133a,d upon dimerization.

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