Homotopic, Enantiotopic, and Diastereotopic

Consider the CH2 group of 2-butanol. There are no symmetry operations in 2-butanol, and as such the two hydrogens of the CH2 cannot be interconverted by a symmetry operation. Therefore, these two hydrogens are expected to be different from one another in all meaningful ways, such as NMR shift, acidity, C-H bond length, bond dissociation energy, reactivity, etc. They have the same connectivity, but there is no symmetry operation that interconverts them in any conformation. They are stereoheterotopic, and defined specifically as diastereotopic. 

Now consider the CH2 group of propane. There is, or more properly can be, a C2 operation that interconverts the two hydrogens, and so they are considered to be equivalent. The modern terminology is homotopic, and is defined as interconvertable by a C axis of the molecule. These hydrogens are equivalent in all ways. 

Homotopic groups remain equivalent even in the presence of a chiral influence. Since chiral molecules need not be asymmetric (they can have C axes), groups can be homotopic even though they are part of a chiral molecule. Consider the chiral acetal shown in the margin. The methyl groups are homotopic because they are interconvertable by a C2 operation. A chiral influence cannot distinguish these methyl groups. 

Another common situation where topicity issues become important is at trigonal centers, such as carbonyls and alkenes. As some examples, let s focus on carbonyl groups. The two faces of the carbonyl are homotopic in a ketone substituted by the same groups [R(C=0)R], such as acetone, because the molecule contains a C2 axis (see below). The faces are enantiotopic in an unsymmetrically substituted ketone, such as 2-butanone, because they are interconverted by a a plane. The faces are diastereotopic in a structure such as either enantiomer of 3-chloro-2-butanone, because there are no symmetry elements that interconvert the faces. 

Chiral molecule with homotopic methyl groups 

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Students are familiar with the terms applied to relationships between stereoisomeric molecules homomeric molecules (superposable molecules), enantiomeric molecules (nonsuperposable mirror images), and diastereomeric molecules (stereoisomers that are not mirror images of one another). These familiar terms are parallel to the terms that we have introduced above homotopic, enantiotopic, and diastereotopic, which are applied to nuclei or groups within the molecule. 

For definitions of homotopicity, enantiotopicity and diastereotopicity see Mislow and Raban (1967) and Jennings (1975). 

FIGURE 5.58 Replacement tests for homotopic, enantiotopic, and diastereotopic hydrogens. 

Topicity (from the Greek root topos meaning place or local) is important because it allows us to prediction the number of unique chemical shifts we expect to see from the resonances of a particular molecule. Groups or atoms related by symmetry come in three varieties homotopic, enantiotopic, and diastereotopic. 

In order to discuss facioselectivity concisely, cate needs to classify molecular faces (half-spaces). - In 1975, we categorized time-resolved/time-averaged planar stereotopic molecular faces into homotopic, enantiotopic, and diastereotopic classes." ... 

Table 13.1 (p. 134) summarizes the five modes of vectoselectivity at all homotopic (hi-h6), enantiotopic (e), and diastereotopic (di-d4) faces. In Figures 13.22-13.24 are shown examples of vectoaselective, vectononselective and vectoselective transformations of molecules with homotopic, enantiotopic and diastereotopic faces,respectively. 

Label the pairs of protons shown in boldface in each of the following compounds as homotopic, enantiotopic, or diastereotopic, as required. Assume normal rotational barriers and observations at room temperature. 

Characterize the indicated protons as (1) homotopic, enantiotopic, or diastereotopic and (2) magnetically equivalent or nonequiva lent (by the coupling-constant criterion). In parts (h) and (i), the Cr(CO)3 ligand remains on one side of the benzene ring. 

Stereoheterotopic A term that includes both enantiotopic and diastereotopic atoms, groups and faces. Equivalent atoms, groups and faces would be homotopic. 

How to decide if two groups are homotopic, enantiotopic or diastereotopic Stereoselectivity and stereospecificity The Structures We Draw... 

Homotopic Ligands that are related by an n-fold rotation axis. Similarly, faces of a trigonal atom that are related by an n-fold rotation axis. Replacement of any of the ligands or addition to either of the faces gives an identical compound. See also heterotopic, enantiotopic, and diastereotopic. 

D,D% F, F faces - as in discussions of intermolecular selectivity (Figure D.4). The literature a/p system is inapplicable to these acyclic systems. Furthermore, the literature Re/Si (relsi), B/N (b/n) systems do not differentiate between enantiotopic faces, on the one hand, and diastereotopic faces, on the other. Thus, whether it is the enantiotopic faces of iii, or the diastereotopic faces of iv and v, the faces are described by the same Re/Si and B/N descriptors. In contrast, in the novel HED system, iii has enantiotopic faces E / 3, iv possesses diastereotopic faces D/F, and v incorporates chirodiastereotopic faces D /F. Thus, the HED system (a) identifies the relative stereotopicity of the paired faces, including homotopic ones, (b) differentiates between enantiotopic and diastereotopic faces, and (c) reveals the chirality of the molecular field - e.g. homotopic vs. chirohomotopic (i vs. ii), and, diastereotopic vs. chirodiastereotopic (iv vs. v). 

Kaloustian, S. A. Kaloustian, M. K., /. Chem. Educ., 1975,52,56. The terms related faces and unrelated faces, in the latter paper, are hereon replaced by stereotopic faces and not-stereotopic faces, respectively. Stereotopic faces are homotopic, enantiotopic, or diastereotopic. Not-stereotopic faces are astereotopic or nonstereotopic (see Volume 1, Chapter 1). Molecular faces of the same moiety are considered paired paired faces of a molecular moiety/molecule are, by virtue of the pairing, always stereotopic. 

Identify the labeled groups as homotopic, enantiotopic, or diastereotopic, and determine whether the indicated hydrogens are pro-R or pro-S (or neither). 

Label the sets of connectively equivalent sets of protons in the molecules (a)-(j) according to whether they are homotopic, enantiotopic, or diastereotopic. Using Tables 8.3 and 8.4, predict the approximate chemical shifts, in 8, and the splitting patterns expected for each chemically distinct type of hydrogen atom that you identify. Assume in this analysis that the coupling constants of all nearest neighbors are identical. 

FOR EACH OF THE FOLLOWING COMPOUNDS, IDENTIFY THE FiELATIONSHIP BETWEEN THE TWO INDICATED PROTONS (ARE THEY HOMOTOPIC, ENANTIOTOPIC OR DIASTEREOTOPIC ) AND DETERMINE WHETHER THEY ARE CHEMICALL Y EQUI VALENT. 

Constitutionally Heterotopic and Diastereotopic Groups Differ in all scalar properties and are distinguishable under any conditions, chiral or achiral. Asymmetric molecules cannot contain homotopic or enantiotopic groups, only diastereotopic or constitutionally heterotopic groups. 

Nuclear magnetic resonance chemical shift differences can serve as an indicator of molecular symmetry. If two groups have the same chemical shift, they are isochronous. Isochrony is a property of homotopic groups and of enantiotopic groups under achiral conditions. Diastereotopic or constitutionally heterotopic groups will have different chemical shifts (be anisochronous), except by accidental equivalence and/or lack of sufficient resolution. 

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