Cyclopropanes optical rotations

A. Semiempirical Descriptions of Optical Rotations of Cyclopropanes by the Triad Theory of Optical Rotations... 

In the literature there exists several theoretical approaches to deal with optical rotations [0]d of (monocyclic) chiral cyclopropanes 1 . In formula I R corresponds to a substituent R attached to the ligand-site i. The enumeration of the skeletal carbon atoms is... 

All these shortcomings are overcome by the triad theory of optical rotations (TTOR approach) The TTOR approach is a semiempirical theory of optical rotations of (arbitrary) organic compounds in the transparent region (X 300 nm for cyclopropanes). The theory may be developed in terms of expressions which have a particularly simple mathematical form and which, furthermore, meet the chemists way of thinking in terms of substituent effects . The mathematical expressions contain only formally defined elements, such as ligand-specific parameters ( rotation parameters ) 2(R ), v(R ), etc. These sub-... 

FIGURE 1. Elements of optical activity (EOA) for the description of optical rotations of cyclopropanes referring to the configurational level of representing molecules... 

In Ref 4 it has been shown that for a numerically adequate description of optical rotations of cyclopropanes I in the standard solvent chloroform a restriction to the terms and suffices, i.e. the optical rotations of I can be described in terms of helix optical... 

The helix contribution is given by equation 3. In equation 3 A(R ) is a ligand-specific parameter which characterizes the optical rotation of a RCCR -helix of cyclopropanes I. 

The restriction of the theoretical treatment of optical rotations of cyclopropanes I to the basis of equations 2, 3 and 5 has several implications with regard to the descriptions of molecules on the conformational level. A discussion of some special cases shall demonstrate that the success of equation 2 does not mean that for the theoretical treatment of optical rotations only the configurational level for representing molecules is relevant. On the contrary, an adequate description of optical rotations of organic compounds must take the various conformations of the compounds and the conformer equilibria explicitly into account The very point is that, due to favorable conformational equilibria, often rotation contributions from conformational effects are small or cancel (to a large extent). 

The resume of the above outline is that the success of equations 2,3 and 5 is often due to the fact that optical rotation contributions from substituents attached to the cyclopropane skeleton can be neglected as a result of cancelling effects. Hence, a discussion of... 

More insights into the substituent effects which are responsible for the generation of helix optical rotations of cyclopropanes I can be obtained through a dual substituent parameter (DSP) approach Referring to the polar substituent constant (which... 

The other parameter, /x(R), which describes the C2v-tetrahedral contribution to the optical rotations of cyclopropanes I is related to the distance Xqj between the asymmetric carbon atom and the center of the polarizability in the C-R unit. ... 

FIGURE 2. Correlations between the parameters to calculate helical optical rotations of allenes, Ay (R), and cyclopropanes, A(R)... 

In Ref. 4 comparisons between theoretical and experimental molar rotations of a large number of cyclopropanes are presented. In the following subsections an arbitrary selection from these results will be presented. The predictions of optical rotations simultaneously provide determinations of absolute configurations. 

For the cu-disubstituted cyclopropanes IV the optical rotation results from only the C2,-tetrahedral SOA i.e. from atomic asymmetry according to equation 10. 

Only the methoxy- and chloro-compounds (38, 3 ) exhibit large deviations between calculated and observed rotations. In general, the 1,1-diphenylcyclopropanes XVIII have rather large optical rotations ( [ ]d > 90°). Inspection of Table 3 reveals that the molar rotations of XVIII are almost entirely due to helix optical activity ( 0 q > 0 d ). This is in contrast to an earlier assumption which has attributed optical rotations of XVIII to atomic asymmetry. Further comparisons between calculated and observed optical rotations of complex cyclopropanes I are presented in Table 4. 

As a summary (of the results of Tables 2-4 and those of Ref 4) one may state that the TTOR approach in its truncated form (equations 2,3 and 5) gives a satisfying quantitative description of optical rotations of complex cyclopropanes I. There are only some very few discrepancies between calculated and observed rotations. The disagreements are mostly due to defined unfavorable ligand orientations which may introduce solvent effects (e.g. 

Further optical rotations of cyclopropanes measured at different wavelengths in the transparent region are found in Refs lOa-lOc, 15b, 28, 36, 41, 53. 

So far, optical rotations of compounds have been discussed where the optical activity is associated with the particular structure of the cyclopropane ring. This means that the rotations are generated by a chiral arrangement of (achiral) ligands attached to the (achiral) molecular skeleton. For certain substituent patterns of I, in particular, the rotations are induced by atomic asymmetry. This is true for III and IV. The effect of the (achiral) cyclopropane moiety (viewed as a ligand) on open-chain molecules with an asymmetric carbon atom can be seen from the rotations of (S)-( —)-l-methyl-1-(1-ethoxyethyl) cyclopropane (80) and its counterpart 81 with only acyclic substituents. ... 

If one analyzes the rotation of D-a-(methylenecyclopropyl)glycine (82) the optical activity must come from (at least) four sources. One rotation contribution is associated with the atomic asymmetry of the open-chain moiety (methylenecyclopropane being viewed as a ligand). On the other hand, optical activity will also be induced by the asymmetric carbon atom of the ring and the asymmetry in the electron density distribution of the exocyclic double bond system (with diastereotopic faces). Finally also helix optical activity may be operative. The example of 82 demonstrates the complexity of the optical rotation of an apparently simple cyclopropane derivative. Further discussions of optical rotations of similar compounds, therefore, will cling to only the qualitative level. 

The effect of the type of unsaturated moiety exocyclic to a cyclopropane ring on the optical rotation is demonstrated by the methylenecyclopropane 91 and the vinylidene-cyclopropane 92 Both compounds have the same absolute configuration, (R)-( —). 

The conjugation effect of the cyclopropane ring on optical rotation can also be seen in other situations. If in bicyclic compounds the cyclopropane moiety comes into a,)5-position relative to a double bond, a marked increase in the magnitude of the rotation is observed. This can be demonstrated referring to (— )-cis-carane (99-c), (+ )-trans-carane (99-t) and the cis and irons compounds 100-c and 100-t . 

Isotopic substitution, in particular, deuteration of the cyclopropane ring, induces small but distinct effects on the optical rotation. The simplest chiral deuterated compound is cyclopropane-l,2-d2 (103) (which was obtained from 79 with ases — l H2°(neat, 1dm)). For 103 no specific rotation is available, as the density is not known. 

Increasing the number of deuterium atoms at the cyclopropane ring has no significant effect on the optical rotation. For instance, trans-l-phenylcyclopropane-2,3-d2 (106) exhibits a rotation value in line with those of the other phenyl compounds. The effect of... 

W. Runge, Substituent Effects on Optical Rotations. 6. The Triad Theory of Optical Rotations of Cycle Molecules Cyclopropanes, ISS-Report (CHE-RU-83-06), Heidelberg, 1983. 

Chiral malonate esters have been used successfully in asymmetric cyclopropanations, as shown by the example in Scheme 6.39, part of a total synthesis of steroids such as estrone [143,144]. The key step in this sequence is an intramolecular Sn2 alkylation of the monosubstituted malonate. The rationale for the diastereoselec-tivity is shown in the illustrated transition structure. Note that the enolate has C2 symmetry, so it doesn t matter which face of the enolate is considered. The illustrated conformation has the ester residues syn to the enolate oxygens to relieve Al>3 strain, with the enolate oxygens and the carbinol methines eclipsed. The allyl halide moiety is oriented away from the dimethylphenyl substituent, exposing the alkene Re face to the enolate. The crude selectivity is about 90% as determined by conversion to the dimethyl ester and comparison of optical rotations [143], but a single diastereomer may be isolated in 67% yield by preparative HPLC [144], This reaction deserves special note because it was conducted on a reasonably large scale ... 

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