Chirality 2” rule

The diene chirality rule (hereafter referred to as DR) constitutes a simple tool for correlating the sign of the lowest energy tt —> n transition (] A —> 1B in C2 symmetry) of the distorted diene to the chirality (left or right-handed) of the chromophore. The validity of this rule is based on the assumption that the CD of the distorted chromophore is determined by its intrinsic helicity alone and that external dissymmetric perturbations have only minor effects on the optical activity. 

The intrinsic contribution, accounted for by the diene rule, seems to be easily outweighed by the perturbations arising from the allylic axial substituents, which in turn define the allylic axial chirality rule. This latter can be formulated in two ways The olefin-picture , where chirality is referred to the nearest double bond, and the diene-picture ,... 

A useful method for the establishment of the absolute configurations of chiral primary amines involves formation of their salicylidene derivatives and application the salicylidcnamino chirality rule 172. Other procedures for primary amines are based on, either the CD of their V-(2,4-diniirophenylsulf enyl)- V-(4-methylphenylsulfonyl) derivatives as described in Section 4.3.4.I.5.251, or on the exciton chirality method313. 

Alternatively, the absolute configuration of dihydrodiol derivatives of arenes can be established by the application of the dibenzoate chirality rule to the bis(4-dimethyloaminobenzoate) or bis(4-dimethylaminocinnamate) derivative (Section 4.4.2.4.1.). 

The dibenzoate chirality rule 155, 156 extends the application of the exciton chirality method to molecules containing no suitable chromophore, but, rather two hydroxy groups which can be converted to benzoates or cinnamates. For example, the dibenzoate 1, obtained by benzoy-lation of the ra-diol, from microbial oxidation of ethylbenzene, displays a negative exciton Cotton effect and is hence assigned the 1 S.2R configuration157. 

The amplitude (A) of the exciton Cotton effect is inversely proportional to the square of the interchromophoric distance. Thus, weak exciton split Cotton effects are expected for remote dibenzoates. Nevertheless, exciton Cotton effects were used for the assignment of the configuration of dibenzoates in a steroidal skeleton separated by as many as seven or eight C—C bonds158. In one application, the absolute configuration of Wieland-Miescher ketone (—)-2 was established by the use of the dibenzoate chirality rule for the 4-bromobenzoylated derivatives of the epimeric 1,5-diols 3 and 4, obtained by reduction of (-)-2159. 

The absolute configurations of two rigid cyclic diols, (—)-adamantane-2,6-diol and ( )-spiro[5.5]undecane-3,9-diol, have been determined by the application of the dibenzoate chirality rule to the bis(p-methoxybenzoate) derivatives195,196. 

Due to the complexity of conformational equilibria, the application of the dibenzoate chirality rule to determination of the absolute configuration of acyclic diols and polyols requires cautious evaluation of the CD data. For example, (0,0)-dibenzoyl derivatives of diesters and N.N.N ,AT-tetraalkyldiamides of (/t,f )-tartaric acid give exciton Cotton effects of opposite sign due to the preference of diesters for a planar and tetraalkyldiamides for a gauche conformation of the carbon chain176. 

The dibenzoate chirality rule 153,156 (Section 4.4.2.4.1.) allows determination of the absolute configuration of dibenzoylated amino alcohols186 187 198, mercapto alcohols188 and diamines187. For acyclic /1-amino alcohol O.A-dibcnzoate derivatives the dominant rotatory... 

While the even-numbered cumulene gives (Z)-111 of C2y symmetry and ( )-112 of C2h symmetry, the odd-numbered cumulene gives two enantiomers 113 and 114 both of C2 symmetry. Bridging these two substituents A and A in 113 or 114 by a chain gives rise to a single-bridged allene of C2 symmetry whose chirality can be specified following the axial chirality rule 11 ... 

Application of the exciton chirality rule has allowed the assignment of configuration (+ )-trans-(4R,5R) to dihydroxy-4,5-dihydrobenzo[a]pyrene (357), a mammalian metabolite of benzo[a]pyrene.217 Thus the prominent enantiomer of the 4,5-dihydrodiol formed from benzo [a] pyrene by rat-liver microsomes has the configuration (4R,5R) in contrast to the earlier report that the configuration was the opposite one.218 Consequently, ( + )-(358) has a (4S,5R) configuration. This epoxide is a better substrate for epoxide hydrolase than its enantiomer and has 1.5-5.5-fold less mutagenic activity as compared to the (—) enantiomer. 

Our next section will deal with symmetry rules for chiral olefins. Before introducing these rules we would like to present another molecule whose spectra will serve later as a warning for the use of chirality rules. This molecule is limonene, whose absorption and CD spectra were measured41 in the VUV region in the gas phase. In addition, the... 

FIGURE 16. The exciton chirality rule relates the torsion angle or helicity of two electric dipole transition moments (<--->) to the signed order of the CD Cotton effects... 

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