Achiral meso-configuration

Exercise 5-14 From the compounds listed select all those that may have achiral meso configurations and draw the configurations for each of them. 

Saalfrank and coworkers reported the synthesis of some triple helicates of Fe(III) using tailor-made tetradentate ligands with m-phenylene H2[ll] and m-pyridylene H2[12] spacers (Scheme 5.5). The free-guest triple helicates [Fe2(ll)3] (5.12) and [Fe2(12)3] (5.13) were obtained as racemate with (A, A) or (A, A) configurations at the metal centre and were defined as a metallotopomer of 2-cryptands. Interestingly the related helicates [Kc(Fe2(12)3)][PF6] (5.14), with a guest cation inside the cavity, exhibited achiral meso-configuration (A, A) at the metal centres. The latter were defined as metallotopomer of... 

An interesting case is the assignment of configuration for rac-methyl (2R, 3R )-2,3-dimethyl-5-oxohexanoate (5 on p469) by correlation with 2,3-dimethy1-1,4-butanediol and 2,3-dimethylbutanedioic acid (see step 6 - 7, p 469). The stereogenic centers are not touched and still the correlation leads from chiral to achiral (meso) compounds8. 

Similarily, the 4,14-dicarboxylic acid 56 with C2-symmetry could also be resolved via its 1-phenylethylamine salts and its configuration unambiguously correlated with the monocarboxylic acid 55 through the monobromo derivative 5878). Accordingly 55 and 56 with the same sign of optical rotation have the same chirality. Many racemic and optically active homo- and heterodisubstituted 4,12- and 4,14-disubstituted [2.2]metacyclophanes have been prepared and chemically correlated 78,79) mainly to study their chiroptical properties78). Whereas 4,12-homodisubstituted compounds have a center of inversion ( -symmetry) and are therefore achiral meso-forms , the corresponding 4,14-isomers are chiral with C2-symmetry. All heterodisubstituted products are chiral (Q-symmetry see also Section 2.9.4 for the discussion of their chiroptical properties and their use as models for the application of the theory of chirality functions). 

Of these, 11 is achiral (meso), whereas 10 is chiral. Therefore, by simply determining which oxidation product is optically active, and hence chiral, we can assign the configurations of 8 and 9. Direct comparison of these synthetic aldopentoses with the naturally occurring compounds then could be used as proof of the structure of natural aldopentoses. By this reasoning 8 turns out to be D-arabinose and 9 is D-ribose. 

The chirality of (d) depends on the configuration at both of the chirality centers. The (R.R) and (5,5) isomers are chiral enantiomers the (R,S) isomer is an achiral meso compound. 

H-nmr spectroscopy readily enables the differentiation of chiral from achiral (meso) diastereoisomers of 3,5- and 2,6-dimethyl-4-phenylpiperidines because in the meso forms the two methyls have identical environments and give rise to the same resonance, while chiral isomers involve an axial-equatorial pair that results in two separate methyl signals (see 39). The configurations of both the chiral 2,6- and 3,5-dimethyl reversed ester analogs of pethidine have been confirmed by X-ray crystallography/27 41)... 

Solution 13 The three configurational stereoisomers of 1,2-dimethylcyclopentane are shown here. Both trans stereoisomers are chiral, while the cis configuration is an achiral meso compoimd. 

The equilibrium ensemble of the configurations of meso-tartaric acid 10 a—c has umin = 0. From the definition of umm follows immediately that for all achiral molecules min = 0 holds. This applies also to those cases where asymmetric C-atoms are present but cancel each other because of overall molecular symmetry. 

In principle, separation of resonances of diastereomeric compounds (such as dl and meso isomers) may be increased simply through use of an appropriate achiral solvent. Chiral solvents may in some cases be especially effective in producing a separation, particularly if the diastereomers differ in configuration about a center that is amenable to analysis by the CSA method. Kaehler and Rehse (89) give a detailed account of conditions necessary for measurement of the ratio of meso- and dZ-tartaric acid employing A,N-dimethyl PEA. Bomyl acetate used as solvent for l,2-difluoro-l,2-dichloroethane (90) allows measurement of the diastereomeric composition. Paquette and co-workers (91,92), using TFAE, were able to determine the diastereomeric purity of the recrystallized adducts 47 of... 

This phenomenon of chirality degradation is carried to the extreme in the polymerization of (-F)-rrinactive polymer One of the two equivalent asymmetric atoms inverts its configuration during polymerization giving rise to a monomer unit with eiythro or meso strac-ture. The isotactic polymer, 40, so formed is clearly achiral (280). 

Structures VII and VIII are identical because rotating either one 180° in the plane of the paper makes is superposable with the other one. VII possesses a symmetry plane and is achiral. Achiral stereoisomers which have chiral centers are called meso. The meso structure is a diastereomer of either of the enantiomers. The meso structure with two chiral sites always has the (RS) configuration. 

The R,S system is quite general and has many advantages (and a few disadvantages) compared with the d,l notation for simple molecules. For diastereomers, it provides much clearer notations than meso, erythro,1 and threo1 that have been used for many years to designate the configurations of achiral and chiral diastereomers having two chiral carbon atoms ... 

C is correct. Compound E is achiral, and is not the meso compound because D Is (see question 26). Answer A is meso. Answer choice B could not have been formed because there is a change in relative configuration about the original chiral compound. Answer D is chiral. Only answer choice C is left. 

In achiral media, different NMR spectra are expected for each of the four types of enantiomeric pairs and for the two meso compounds. In general, because of the synthetic approach, the ratio of cis- to /nmv-rcsiducs is about three, which, assuming that quaternisation at one tetrahydroisoquinoline residue does not affect quaternisation at the other, leads to proportions of cis-cis, cis-trans and trans-trans isomers in the approximate ratio of 11 6 1. The preference for cis-residues has been proved by using nuclear Overhauser effect NMR measurements and by X-ray crystallography on related substances [37,38]. The H NMR chemical shifts, principally of the H8 proton, can be affected not only by whether the C1-N2 configuration in the residue is cis or trans but also by the configuration of the remote tetrahydroisoquinoline unit. 

There are no stereogenic centers. Both molecules have planes of symmetry. The cis isomer has two such planes, through opposite corners of the ring. The trans isomer has one such plane, through the opposite methyl-bearing corners. Both compounds are optically inactive and achiral. They are not meso compounds because there are no chiral centers. To summarize, the two isomers are configurational, achiral and diastereomers. 

The dicarboxylic acid obtained as the product is a meso form, with a plane of symmetry shown by the dashed line. Therefore, this acid is achiral. (Experiments such as this were helpful in assigning configurations to the various monosaccharides.)... 

There are six isomers of difluorocyclobutane (see below). The vicinal di-substituted isomers B and C (both with a twofold proper axis of symmetry, symmetry point group C2) are chiral and are enantiomers of each other. The cis-configured compound D (with a plane of symmetry, symmetry point group Cs) is achiral and is a meso compound. The compounds A and F (both with two planes of symmetry and on the line of intersection of both planes a twofold axis of symmetry, symmetry point group C2V) and E (with a plane of symmetry, a twofold axis of symmetry perpendicular to it and a centre of symmetry, symmetry point group C21O are all achiral. These results can be verified from the flow chart given in the appendix. 

Compounds that are achiral even though they have asymmetric carbon atoms are called meso compounds. The (2R,3S) isomer of 2,3-dibromobutane is a meso compound most meso compounds have this kind of symmetric structure, with two similar halves of the molecule having opposite configurations. In speaking of the two diastereomers of 2,3-dibromobutane, the symmetric one is called the meso diastereomer, and the chiral one is called the ( ) diastereomer, since one enantiomer is ( + ) and the other is (-). 

The meso stereoisomer of tartaric acid is achiral, and possesses two self-cancelling stereogenic centres of opposite configuration. 

As the number of stereocenters in a molecule increases, the number of possible diastereomers increases. A molecule with four dissimilar stereocenters, for example, can exist as one of sixteen stereoisomers. Of these sixteen stereoisomers there are four pairs of enantiomers, and the remaining four pairs are diastereomers. Molecules with configurational diastereomers also arise from many systems other than those with stereocenters. One of the most common examples is a double bond that is substituted in such a way that diastereomers exist. Any combination of two or more molecular features that give rise to stereoisomers will always produce diastereomers, whereas sources of chirality are needed to produce enantiomers. Because stereochemistry can have a high impact on molecular properties, diastereomers generally have easily discernable differences in their physical and chemical behaviors. Some molecules possess greater than or equal to two tetrahedral stereocenters and are nonetheless achiral. These are called meso stereoisomers. These occur when the internal symmetry of the molecule makes it superimposable on its mirror image. 

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