Octant rule applications

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. 

The octant rule has been tested by various theoretical approximations12-18 and thoroughly empirically analyzed by Kirk and Klyne19 22. Two generalizations of importance with regard to configurational applications of the octant rule can be given. 

Cotton effects due to unsymmetrical heteroatom ring-substituted cyclohexanones have also been recorded34. However, direct application of the octant rule to determine the absolute configuration of heterocyclohexanones such as 8 is not recommended30. 

The CD of fenchone (77), where the applicability of the octant rule is not obvious, and its sulfur and selenium analogues have been compared178. 

In order to use its CD to determine the AC of a chiral molecule, a theory is required which predicts the sign of the CD of a given enantiomer. The utilization of CD by organic chemists was greatly stimulated by the development of the Octant Rule, which predicts the CD of the n-tt electronic excitation of carbonyl functional groups [3], Subsequently, so-called Sector Rules were developed for many other electronic chromophores, extending the applicability of CD [4],... 

D. A. Lightner, The octant rule, in Circular Dichroism Principles and Applications, 2nd edn, Wiley-VCH, New York, 2000. 

Determination of absolute configuration by CD. Applications of the Octant Rule and the Exciton Chirality Rule... 

However, some ketones, such as 1-keto and 11-keto steroids have some molecular components lying in front of the carbonyl carbon (even in front of its oxygen), or in front octant regions. Clarification of the boundary between front octants and back octants was the subject of intensive theoretical and experimental studies, [6-11] which led to a clarification on the shape of the third nodal surface as convex (B, Figure 7). For most applications of the Octant Rule it is sufficient to consider only the back octants, and the special circumstances which require consideration of front octants will be obvious from the structure of the ketone. In practical applications of the Octant Rule, the octant diagrams are used to... 

The origins of two chirality rules, the Octant Rule for ketones and the Exciton Chirality Rule, have been explained, and it has been shown how the rules can be applied to the determination of molecular absolute configuration. In applications of the Octant Rule, when the absolute configuration of a ketone is known, the rule may be used to determine its conformation. Applications of the Exciton Chirality Rule to determine the absolute configuration of diols follows from the derivatization with strongly UV-visible absorbing chromophores. 

The Octant Rule followed as a generalization of the axial haloketone rule and was presented, along with many examples, in C. Djerassi Optical Rotatory Dispersion and its Applications to Organic Chemistry, McGraw Hill, New York, 1960. 

Chiroptical Properties O.R.D. and C.D.). A full account of the proposed Reverse Octant Rule for chiral olefins has appeared, and is supported by data for 68 unsaturated steroids. Most endocyclic olefinic steroids conform qualitatively to the rule which, for the lowest energy transition n — n ), reverses the signs of the more familiar carbonyl octant rule. The application of the rule is illustrated (Figure 1) for an oestr-5-ene (6) and a cholest-5-ene (7). The former... 

E heterocyclic derivatives (263)/ The configurations at C(16) were established by hydrolysis to the corresponding ketones (264) and application of the octant rule to the dissymmetric 4-oxoperhydropyridazine system. 

From the very beginning the octant rule ran into difficulties because several (mostly well-defined) observations did not agree with its predictions. Striking examples where the octant rule is in serious conflict with the observations for a whole class of compounds are provided by the conjugated (a, )5)-cyclopropyl ketones. Here, the predicted signs of the (n, 7T ) CE were often opposite to the experimental findings. Therefore, for these types of molecules as an empirical finding an antioctant rule was assumed to be applicable. 

In Ref 105 the (n, n ) circular dichroism of the tricyclic ketones 152-155 was analyzed with the aim to see whether the systems must be viewed as inherently chiral chromophores or rather inherently symmetric chromophores, respectively. If they fall more nearly into the inherently symmetric classification the octant rule should be applicable. As a basis for the classification the order of magnitude of the rotational strengths was used together... 

Application of the normal octant rule ((a) in Figure 14) predicts a negative (n, n ) CE for the abundant s-cis conformer of 15, but a positive one for the less abundant s-trans form. 

Conformational mobility is a serious drawback to application of this Octant Rule. For a compound such as 2oc-azidocholestane, the Rule is applied to each of six rotamers (generally depicted as Newman projections). By a combination of conformational tinalysis and this Octant Rule, one tries either to predict the sign of the rotation from the favoured structure or vice versa. In this particular case, no stereochemically significant conclusion was reached... 

In Figure 3.5 the application of the octant rule to (+ )-3-methylcyclohexanone is demonstrated. In the boat form as well as in the chair form the methyl group is located in a positive octant if it is in an equatorial position and in a negative... 

If viewed from the oxygen, most optically active carbonyl compounds have their substituents only in the rear octants. The appearance of the plane that separates the rear octants from the front octants is not determined by the symmetry of the isolated chromophore. Calculations have shown that it has approximately the shape depicted in Figure 3.4b. Many examples have verified the validity of the octant rule, but there are also cases where it is not applicable, at least not in its original, simple form. This is true for ketones with a cyclopropane ring in the a, jS-position and for fluorosubstituted ketones, for which the experimentally observed sign can be reproduced only if the perturbation due to the fluorine atom is assumed to be smaller than that due to the hydrogen atom. More recent detailed calculations solved some of these problems. (Cf. Charney, 1979.)... 

The remaining problem of the structure of mesembrine, the absolute configuration, was solved by an application of the octant rule (10). The enantiomer XXa should exhibit a negative Cotton effect and mesembrine, dissolved in dioxane did show such a negative effect. 

A full report of the c.d. of steroidal diol bis-(p-dimethylaminobenzoates) confirms the reliability of theoretical calculations of the coupled Cotton effects of the remote ester groups (exciton chirality method). The c.d. curves show two maxima of opposite signs, separated by some 27 nm, and with intensity inversely proportional to the square of the interchromophore distance. The profile of the observed c.d. curve results from the superimposition of two component curves, each of asymmetric shape.A review of the uses of chiroptical techniques for structural and conformational studies includes examples of the assignment of stereochemistry to steroids and terpenoids, among a wide variety of natural products. The Octant Rule for carbonyl compounds and the rules applicable to other chromophoric systems are discussed critically. 

Yamada and Kunieda investigated the application of the octant rule to azabicyclic ketones and found good agreement of the predictions with the experimental results obtained for 1-oxopyrrolizidine of known chirality. ... 

In the CD spectrum of (—)-E, a negative Cotton effect was observed, while (+)-E showed a positive Cotton effect. Accordingly, the octant projection of (-)-E and (+)-E must be as shown in Figure 2.53, and (-)-E was (2/ ,4S)-E, while (+)-E was (2S,4R)-E. This is a typical example of application of the octant rule in determining the absolute configuration of substituted cyclohexanones. 

The Taxane Diterpenes.— The taxane skeleton represents an alternative mode of cyclisation of the macrocyclic diterpene hydrocarbon. Seven new taxane derivatives have been isolatedfrom Taxus baccata and characterised on the basis of spectroscopic and other data. Their structures are summarised in the following formulae (136a—g). In addition, the structure of baccatin-III (137), one of a group of complex esters isolated from the same source, has been com-pleted. The application of the olefin Octant rule to the taxane A double bond leads to the absolute configuration of these diterpenes. 

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