Diastereotopic molecules

Diastereotopic (Section 7 13) Descnbing two atoms or groups in a molecule that are attached to the same atom but are in stereochemically different environments that are not mirror images of each other The two protons shown in bold in H2C=CHC1 for example are diastereotopic One is cis to chlonne the other is trans... 

If a molecule contains several asymmetric C atoms, then the diastereomers show diastereotopic shifts. Clionasterol (28a) and sitosterol (28b) for example, are two steroids that differ only in the absolute configuration at one carbon atom, C-24 Differing shifts of C nuclei close to this asymmetric C atom in 28a and b identify the two diastereomers including the absolute configuration of C-24 in both. The absolute configurations of carboxylic acids in pyrrolizidine ester alkaloids are also reflected in diastereotopic H and C shifts which is used in solving problem 54. 

The presence of asymmetric C atoms in a molecule may, of course, be indicated by diastereotopic shifts and absolute configurations may, as already shown, be determined empirically by comparison of diastereotopic shifts However, enantiomers are not differentiated in the NMR spectrum. The spectrum gives no indication as to whether a chiral compound exists in a racemic form or as a pure enantiomer. 

The concept of heterotopic atoms, groups, and faces can be extended from enantiotopic to diastereotopic types. If each of two nominally equivalent ligands in a molecule is replaced by a test group and the molecules that are generated are diaster-eomeric, then the ligands are diastereotopic. Similarly, if reaction at one face of a trigonal atom generates a molecule diastereomeric with that produced at the alternate face, the faces are 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. 

Identify the indicated protons in the following molecules as unrelated, homotopic, enantiotopic, or diastereotopic ... 

Diastereotopic (Section 13.8) Two hydrogens in a molecule whose replacement by some other group leads to different diastereomers. 

In the discussion of the stereochemistry of aldol and Mukaiyama reactions, the most important factors in determining the syn or anti diastereoselectivity were identified as the nature of the TS (cyclic, open, or chelated) and the configuration (E or Z) of the enolate. If either the aldehyde or enolate is chiral, an additional factor enters the picture. The aldehyde or enolate then has two nonidentical faces and the stereochemical outcome will depend on facial selectivity. In principle, this applies to any stereocenter in the molecule, but the strongest and most studied effects are those of a- and (3-substituents. If the aldehyde is chiral, particularly when the stereogenic center is adjacent to the carbonyl group, the competition between the two diastereotopic faces of the carbonyl group determines the stereochemical outcome of the reaction. 

If two asymmetric atoms are present in the molecule (see 4.1), NMR can still be used to determine the configurational stability but intermolecularly diastereo-topic groups are then used instead of intramolecularly diastereotopic ones. 

The ethyl ester protons are worthy of note in this molecule. Though there is no chiral centre present, these are non-equivalent by virtue of being diastereotopic (remember the Z test ). 

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

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 general subject of asymmetric synthesis has been reviewed extensively (1-5). The term asymmetric synthesis has been defined in more than one way (1,4) however, a useful definition is the one given by Morrison and Mosher (1) a process which converts a prochiral unit [refs. 6 and 7] into a chiral unit so that unequal amounts of stereoisomeric products result. The stereoisomeric products may be enantiomeric or they may be diastereomeric. The substrate molecule must contain either enantiotopic or diastereotopic groups or faces (8,9), since the attack of a reagent at equivalent groups or faces cannot lead to isomeric products. 

The X-ray crystal structure of fZ)-4-[(5)-2,2-dimethyl-l,3-dioxolan -ylmethyl-ene]-2-phenyl-5(4//)-oxazolone has been determined. " The analysis shows an almost planar disposition for the entire molecule with the exception of the dioxolane ring that adopts an envelope conformation. As such, the dioxolane ring is mainly situated on the si,si diastereotopic face of the olefinic bond, a situation that accounts for the observed diastereoselectivity in Diels-Alder reactions. 

A good illustration of the usefulness of the concepts local symmetry and chirotopicity is provided by the case of glycerol. The question as to whether the protons of the C,H20 groups are equivalent is problematic for most professional chemists. The answer is that they are not They are chirotopic (property ) and diastereotopic (relationship ). The issue that leads most chemists astray is the symmetry plane, which is the clue to that the molecule is achiral. However, only atoms within the symmetry plane are achirotopic. those outside are chirotopic. 

In retrospect, it seems unfortunate that in 1971 Morrison and Mosher8 generalized the definition, while keeping the term, an asymmetric synthesis is a reaction in which an achiral unit in an ensemble of substrate molecules is converted by a reactant into a chiral unit in such a manner that the stereoisomeric products arc produced in unequal amounts ( Footnote The substrate molecule must have either enantiotopic or diastereotopic groups or faces) . Obviously the phrase "an achiral unit in an ensemble of substrate molecules is too inexact and requires a great deal of additional explanation, which was partially given by the footnote (note that molecule, i.e., singular, was used ). Currently, the Morrison-Mosher term appears to be equivalent to stereoselective reaction. Unfortunately, this term was only defined in the modem sense by Izumi in 1971, i.e., in the same year the Morrison-Mosher definition was published. 

No. The numbers of molecules with S and R configurations at C are not equal. This is so because the presence of the C -stereocenter causes an unequal likelihood of attack at the faces of C. Faces which give rise to diastereomers when attacked by a fourth ligand are diastereotopic faces. 

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