Patai S., Rappoport Z. 1997 The chemistry of functional groups. The chemistry of double-bonded functional groups / 0155 260

O

−8.0(282), +11.3 (243), −40.0 (200)3 2 4

The structure of 40-propyl-4ˇ,5ˇ-ethenopregnane-3,20-dione (131) as the main product of photochemical [2 C 2] cycloaddition of 1-pentyne to progesterone and 4˛,5˛-analogue 138 was confirmed by X-ray analysis. The CD data of 131 140 were in agreement with A/B-cis and A/B-trans fusion in 131 and 138, respectively, and with the cyclobutene ring (main perturber of the CDO n ! Ł transition) lying in a ( )-octant of 131 and a (C)-octant of 138323.

An unusually strong CD for open-chain ketones 141 was recently reported327. Ketones 141 were formed by hydrogenation of ˇ, -unsaturated precursors ( ε not reported) which were obtained by enantioselective protonation of samarium enolates (Table 8).

The CD of a series of eight differently-substituted analogues of 9,10-ethano-9,10- dihydroanthracen-11-one (142 and 143) was studied experimentally and theoretically329. Alteration of the substituent(s) on the benzene ring(s) affects the transition dipole magnitude and the transition energy of the aromatic chromophore without much change in the polarization direction.

P. Vogel’s group studied exhaustively the 5,6,7,8-tetramethylidenebicyclo[2.2.2]octane system and its metal carbonyl complexes. The preparation and CD spectra of tricarbonyliron complexes (144 147) were reported333. The chirality of complexes 144 and 146 is due uniquely to the coordination of Fe(CO)3 moieties. The signs of the Cotton effects for (C)-144 and (C)-146 obey the octant rule, as the endo-Fe(CO)3 of 144 and 146 fall in a positive octant, while the second exo-Fe(CO)3 (syn to the carbonyl) lies almost on the XY nodal plane, and thus its contribution is expected to be small. The deuterium-substituted free tetraenone 148, however, showed an anti-octant behavior. The CD spectra of 144 and 146 are strongly temperature and solvent dependent.

TABLE 8. CD of ketones 141 in Et2O (corrected for 100% ee)

The CD properties of a number ( 4-polyene) Fe(CO)3 complexes containing carbonyl group have been described336,337. Tricarbonyliron complex of 2,3-dihydrotropone (149) was resolved by HPLC and its absolute configuration determined by X-ray and CD338.

The absolute configuration of homotropone (150) and its Fe(CO)3 complexes was deduced from comparison between experimental and theoretically calculated (CNDO/S) CD of preferred trans conformation339.

FIGURE 15. Typical bisignate exciton coupling CD spectra (upper) and bell-shaped UV (lower) spectra for chromophores with electronic transitions near 300 nm. The shape of the observed CD curve is due to overlapping, oppositely-signed positive and negative CD transitions from electronic excitation into (two) exciton states

their (locally) excited states. These excited-state dipole dipole interactions, which lie at the heart of exciton coupling, are most effective when the electric dipole transitions are strongly allowed as in ! Ł UV-visible transitions. Exciton coupling leads to shifted and broadened, if not split, UV-visible spectra of the composite molecule344. When the chromophores are held in a chiral orientation, exciton coupling is typically seen as two oppositely-signed CD Cotton effects flanking the relevant UV-visible absorption band(s) (Figure 15). The signed order of the CD transitions may be correlated with the relative orientation of the relevant electric dipole transition moment from each chromophore, thereby leading to an assignment of absolute configuration of the composite molecule345.

The correlations comprise the exciton chirality rule, which was derived from nonempirical calculations. It states that when the relevant transition moments are oriented in a positive chirality, the long-wavelength component of the associated exciton couplet can be expected to exhibit a positive Cotton effect (Figure 16). When they are oriented in a negative chirality, the long-wavelength Cotton effect is negative. Thus, from the CD spectrum, one can determine the helical orientation of the transition moments and therefore the absolute configuration of the molecule, if the preferred conformation is known.

Applications of the exciton chirality rule have become numerous during the past fifteen years and claim an extraordinarily high degree of success in predicting absolute configuration15,345. In most applications of exciton chirality to the determination of absolute configuration, the molecule under study is derivatized with a suitable chromophore and its circular dichroism spectra are measured and analyzed. Successful application of the rule depends on knowing which chromophores are interacting and the orientation of the component chromophores’ electric dipole transition moments.

In most of these studies, hydroxyl has been the typical resident functional group, which is derivatized with appropriate acids containing chromophores suitable for exciton coupling. The ideal chromophore would have a very intense UV-visible transition, located in a convenient spectral window, and with the orientation of its electric transition moment being well-defined relative to alcohol R OH bond. One of the most successful has been p-dimethylaminobenzoate, which has an intense (ε ca 30, 000) transition in an

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

easily accessible, generally noninterfering, region (near 310 nm). The associated electric dipole transition moment of charge transfer transition is oriented along the long axis of the molecule, from nitrogen to carboxyl. Although the chromophore might adopt a large number of different conformations (relative to its point of attachment on the chiral molecule) by rotating about the ester bonds, one conformation (s-cis) apparently predominates, and the relevant transition dipoles are thus aligned parallel to the ester R O bond. One can determine the relative helicity (C or ) of the transition dipoles by inspection and assign absolute configuration from the CD spectrum14,15,345.

The cyclohexane ring of trans-1,2-cyclohexanediol (Table 9) adopts a chair conformation, with diequatorial preferred. The two enantiomers exhibit oppositely signed O C C O torsion angles. In the bis-p-dimethylaminobenzoate derivatives, the electric transition moments lie parallel to the alcohol C O bonds. Thus, the relative orientation (helicity) of the two transition dipoles correlates with the signs of the torsion angles. According to the exciton chirality rule, a positive exciton chirality is predicted for the (1S,2S) enantiomer, and a negative exciton chirality is predicted for the (1R,2R) enantiomer in complete agreement with the observed bisignate Cotton effects.

Orientation, proximity and chromophore are paramount considerations in applying the exciton chirality rule. Extrachromophoric considerations are relatively unimportant. Thus the CD spectra of bis-p-dimethylaminobenzoates of 5˛-cholestan-2˛,3ˇ-diol and (1R,2R)-cyclohexanediol (both diequatorial diols with the same absolute configurations) are essentially identical. Other steroid diols, whether with vicinal hydroxyls or very distant hydroxyls, give bisignate CD Cotton effects originating from exciton coupling with a signed order consistent with the exciton chirality rule15,345.

Soon after the original development of exciton chirality method346,347 for steroidal diols, Koreeda, Harada and Nakanishi348 extended its application to exciton interaction between benzoate transition at 230 nm (ε 14,000) and enone ! Ł transition at 230 260 nm (ε 7,000 15,000). The p-chlorobenzoate of 3ˇ-hydroxycholest-5-en-7-one (151, Figure 17) exemplifies the application of this method348. The 3ˇ-hydroxy-enone has a ε typical of the s-trans enone chromophore, and the relative orientation (helicity) of the two interacting dipoles in p-chlorobenzoate 151 is shown in Figure 17. Such positive exciton chirality

FIGURE 17. 3ˇ-Hydroxycholest-5-en-7-one p-chlorobenzoate and its conformation (right) showing the orientation of the p-chlorobenzoate and enone transition dipoles giving a positive exciton chirality

is predicted to give rise to splitting of the CD band into a positive lower-energy Cotton effect and a negative higher-energy Cotton effect, which were experimentally observed: p- chlorobenzoate 151 exhibits ε246 C16.7 and ε221 21.6. In contrast, the corresponding acetate ester is noninteracting and has εmax around 210 nm. Large exciton interactions have also been found between two ˛,ˇ-unsaturated ketone chromophores348.