Horeau effect

The optical purity is usually, but not always, equal to enantiomer excess. In order for the two to be equal, it is necessary that there be no aggregation. It is possible, for example, that a homochiral or heterochiral dimer (see Glossary, Section 1.6, for definitions) would refract the circularly polarized light differently than the monomer (or each other). In 1968 [19] Krow and Hill showed that the specific rotation of (S)-2-ethyl-2-methylsuccinic acid (85% ee) varies markedly with concentration, and even changes from levorotatory to dextrorotatory upon dilution. In 1969 [20], Horeau followed up on Krow and Hill s observation, and showed that the optical purity (at constant concentration) and enantiomer excess of (5)-2-ethyl-2-methylsuccinic acid were unequal except when enantiomerically pure or completely racemic. This deviation from linearity is known as the Horeau effect, and its possible occurence should be remembered when determining enantiomeric purity by polarimetry. 

Imagine you have a sample, A, of an enantiomerically pure compound—a natural product perhaps—and, using a polarimeter, you find that it has an [ajp of a-10.0. Another sample, B, of the same compound, which you know to be chemically pure (perhaps it is a synthetic sample), shows an [aJo of-1-8.0. What is its enantiomeric excess Well, you would have got the same value of 8.0 for the [ajp of B if you had mixed 80% of your enantiomerically pure sample A with 20% of a racemic (or achiral) compound with no optical rotation. Since you know that sample B is chemically pure, and is the same compound as A, it must therefore indeed consist of 80% enantiomerically pure material plus 20% racemic material, or 80% of one enantiomer plus 20% of a 1 1 mixture of the two enantiomers—which is the same as 90% of one enantiomer and 10% of the other, or 80% enantiomeric excess. Optical rotations can give a guide to enantiomeric excess—sometimes called optical purity in this context—but slight impurities of compounds with large rotations can distort the result and there are some examples where the linear relationship between ee and optical rotation fails because of what is known as the Horeau effect. You can read more about this in Eliel and Wilen, Stereochemistry of organic compounds, Wky, 1994. 

Coupling of organolithium generated by enantioselective deprotonation [91], highlighting the Horeau effect [92]... 

There is an important difference between Horeau s and Heathcock s examples in that the aldol reaction generates two chirality elements in the bond-forming step. In principle, analysis of such a reaction requires evaluation of two aspects, i.e., the effect of double asymmetric induction on simple and induced diastereoselectivity. The aldol reaction is not particularly suited for this... 

The procedure is widely applicable and highly reliable. For example, the configuration of bicyclo[2.2.2]oct-5-ene-2-carboxylic acid (6) was correctly assigned applying Horeau s method to bicyclo[2.2.2]octan-2-ol (7) derived from 6. Conversely, on the basis of the octant rule, the wrong sign for the Cotton effect of 8 was predicted (see p 430)235. 

Delepine and Horeau also compared the activating effects of the six platinum group metals on Raney Ni in the hydrogenation of carbonyl compounds. Osmium, iridium, and platinum were the most effective, ruthenium and rhodium followed them, and palladium was the least effective.66... 

Attempts have been made to determine enantiospecific differences between enantiomers and racemates in solution using microcalorimetry [29]. The microcalorimetric method can be used to understand the magnitude of stereoselective interactions that could result from the mixing of solutions of enantiomers of a chiral excipient. The heat evolved or heat of solution (A/T ° ) is measured for the racemate as well as the enantiomers and could be indicative of enantioselective discrimination. However, Horeau and Guette [30] reported that enantioselective interaction in an aqueous medium measured using microcalorimetry may be inconsistent and flawed because of the insufficient purity of the optically active samples used and the insensitivity of the measurement relative to small differences in magnitude of the observed effects. 

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