Anti-open conformation

The pivotal role of the conformational behavior of a cinchona alkaloid (e.g., cinchonidine) in its enantioselectivity was nicely illustrated in the platinum-catalyzed enantioselective hydrogenation of ketopantolactone in different solvents [18]. The achieved enantiomeric excess shows the same solvent dependence as the fraction of anti-open conformer in solution, suggesting that this conformer plays a crucial role in the enantiodifferentiation. As a more dramatic example, the solvent affects the absolute chirality of the product in the 1,3-hydron transfer reaction catalyzed by dihydroquinidine [20]. An NMR study revealed that the changes in the ratio between the two conformers of dihydroquinidine can explain the observed reversal of the sense of the enantioselectivity for this reaction when the solvent is changed from o-dichlorobenzene (open/closed 60 40) to DMSO (open/dosed 20 80). 

Undoubtedly, the modification of the structure of the cinchona alkaloid also has a significant effect on its conformational behavior in solution esters [17] and 9-0-carbamoyl derivatives [21] exist as a mixture of two major anti-closed and anti-open conformers, while C9 methyl ethers prefer an anti-closed arrangement in noncoordinating solvents [17]. Here again, protonation provides the anti-open conformation as the sole stable form [16b]. In addition to the solvent polarity, many other factors such as intermolecular interactions are also responsible for the complex conformational behavior of cinchona alkaloids in solution. 

The conformational preferences of 9-O-carbamoyl cinchona free bases reflect in general those of the native cinchona alkaloids. 6 -Neopentoxy-9-0-tert-butylcarba-moylcinchonidine exists as a mixture of two major anti-closed and anti-open conformers in a 65 35 ratio, whereas upon protonation anti-open conformation has been observed exclusively [62]. 

Using NMR spectra combined with X-ray crystallography and molecular calculations it was shown by Bartok et al. that Cnd, Cn, Qn, and Qnd must exist in their anti-open conformations as modifiers. Rotations around the C4 -C9 and C8-C9 bonds are hindered. Therefore, the alkaloids exist also in the anti-open conformations but they do not have the C8-C9 free rotation and form a rigid structure during adsorption on the surface of Pt-alumina catalyst. 

Some important conclusions can be drawn from the experimental confirmation of the proposed 1 1 [modifier-reactant] chiral complex based on the anti-open conformation of the alkaloid-modifier, which fully excludes the... 

According to molecular modehng (MM) calculations, quinine and quinidine preferentially adopt the syn-closed conformation in the gas phase (Figure 6.4). In apolar solvents, however, anti-open conformations are observed in NMR spectroscopy for both quinine and quinidine [13]. More advanced ah initio calculations revealed that the anti-open conformer is preferred in apolar solvents, whereas polar solvents favor the two closed conformers, syn-closed and anti-closed [14]. However, many other factors (such as intermolecular interactions) are likely to influence the complex conformational behavior of cinchona alkaloids in solution. In addition, protonation of the quinucUdine nitrogen atom is reported to hinder rotation about the C4-C9 and C8-C9 bonds [15]. 

Substituents at C9 play a key role in determining the conformation of cinchona alkaloids. For example, esters are present in the anti-closed form in solution, while C9 methyl ethers prefer an anti-open conformation. Recently, the conformations of cinchona alkaloids with a CF3 and a hydroxyl group at the C9 position were examined with NMR spectroscopy [16]. The CF3 group was observed to act as a conformational stabilizer by decreasing the rate of rotation around the C4 -C9, thus allowing the syn and anti conformers to be differentiated at room temperature. The anti conformer was observed to be stabilized by polar solvents with the exception of D2O, in which the syn conformer appeared to be preferred. As found for natural cinchona alkaloids, the syn conformer dominates in apolar solvents. 

The fluorescence spectrum of the nonsteroidal anti-inflammatory agent piroxicam 21 has been determined in a variety of solvents (Scheme 7) <1999PCP4213>. The key observations are that the molecule exists with a strong H-bond between the phenolic OH and the adjacent amide. A very high Stokes shift in the excited state was observed and attributed to the proton-transfer event (tautomerization) between the phenolic and amide oxygens (cf. 21 —>63). In the case of protic solvents, such as water, the open conformation 64 was observed. 

State was attained. After UV-light irradiation, about 80% of the absorbance at 580 nm was recovered. The conversion of 80% from 2a to 2b was almost the same as that in the solution phase. The conversion of the film prepared from 2a solution was 40%, which is half of the conversion of the film prepared from a solution of the closed-ring form isomer. This difference in the maximum conversion to 2b is caused by the conformation of the open-ring form isomers. The isomer has two conformations, anti-parallel and parallel conformations. The former is photoactive whereas the latter is inactive, and half of the open-ring form isomers are in the inactive parallel conformations in solution. Half of 2a molecules in the film prepared from 2a solution are in the inactive parallel conformation. The conformational change is difficult in the amorphous film below Tg. In contrast, 2a in the bleached film prepared from the solution of 2b is in an anti-parallel conformation, and the maximum conversion to 2b at the photostationary state is about two times larger than that in the film prepared from 2a solution. A similar increase in the conversions in the film prepared from the closed-form isomer has been observed in amorphous diarylethenes, 3-10. It should be noted that heat treatment of the bleached 7a film at a temperature above Tg resulted in a decrease in the maximum conversion, which indicates that conformational change takes place at temperatures above Tg. 

As can be seen, conformational changes in Cn are possible by rotation around the C4 -C9 and C8-C9 bonds. It should be noted, that in the case of adsorption of the quinoline portion of the alkaloid on Pt, rotation along the C4-C9 bond is possible but hindered. But in the case of a-iCn, rotation along the C8-C9 bond is excluded, therefore, a-iCn exists only in the anti-open steric hindered conformation. 

D gamma- iQnd in anti-open complex conformation (Bartok et al. ). 

The size of mesoporous silica MCM-41 can be adjusted by changing the number of carbon atoms in surfactant micelles used in the hydrothermal synthesis. Iwamoto and co-workers have reported photocyclization of diarylethenes 124 in different-sized MCM-41. Only the anti-parallel conformation of open form 124 can undergo cyclization upon irradiation to give closed form 125. The reaction rate of 124 was found to be remarkably dependent on the amount of 124 loaded as well as the pore diameter of MCM-41 s, but be independent of the organic groups on the surface of MCM-41s. °... 

Figure 14.3 Anti-open active conformer for catalyst CPD and P-ICPD, and plausible stereochemical model.

TPTTC, TPTBC, and BTPTC were almost 100% in solution and 0.68,0.36, and 0.77, respectively, as amorphous films. Next, the photocyclization was studied using the amorphous films of die open-forms with only the ap-conformation, which were obtained fixim the 100% cyclized amorphous films of TPTTC-c, TPTBC-c, and BTPTC-c by irradiaticm with visible light (>S80 nm). The results that the Yp values for these films (0.69, 0.38, and 0.79, respectively) are almost the same as those for die corresponding films obtained by spin coating from the solution of the unirradiated conqwunds of the open fmm indicate that almost all molecules take up the anti-parallel conformation. ° ... 

If the carbanion has even a short lifetime, 6 and 7 will assume the most favorable conformation before the attack of W. This is of course the same for both, and when W attacks, the same product will result from each. This will be one of two possible diastereomers, so the reaction will be stereoselective but since the cis and trans isomers do not give rise to different isomers, it will not be stereospecific. Unfortunately, this prediction has not been tested on open-chain alkenes. Except for Michael-type substrates, the stereochemistry of nucleophilic addition to double bonds has been studied only in cyclic systems, where only the cis isomer exists. In these cases, the reaction has been shown to be stereoselective with syn addition reported in some cases and anti addition in others." When the reaction is performed on a Michael-type substrate, C=C—Z, the hydrogen does not arrive at the carbon directly but only through a tautomeric equilibrium. The product naturally assumes the most thermodynamically stable configuration, without relation to the direction of original attack of Y. In one such case (the addition of EtOD and of Me3CSD to tra -MeCH=CHCOOEt) predominant anti addition was found there is evidence that the stereoselectivity here results from the final protonation of the enolate, and not from the initial attack. For obvious reasons, additions to triple bonds cannot be stereospecific. As with electrophilic additions, nucleophilic additions to triple bonds are usually stereoselective and anti, though syn addition and nonstereoselective addition have also been reported. 

In open-chain compounds, the molecule can usually adopt that conformation in which H and X are anti periplanar. However, in cyclic systems this is not always the case. There are nine stereoisomers of 1,2,3,4,5,6-hexachlorocy-clohexane seven meso forms and a dl pair (see p. 161). Four of the meso compounds and the dl pair (all that were then known) were subjected to elimination of HCl. Only one of these (1) has no Cl trans to an H. Of the other isomers, the fastest elimination rate was about three times as fast as the... 

Syn elimination and the syn-anti dichotomy have also been found in open-chain systems, though to a lesser extent than in medium-ring compounds. For example, in the conversion of 3-hexyl-4-d-trimethylammonium ion to 3-hexene with potassium ec-butoxide, 67% of the reaction followed the syn-anti dichotomy. In general syn elimination in open-chain systems is only important in cases where certain types of steric effect are present. One such type is compounds in which substituents are found on both the P and the y carbons (the unprimed letter refers to the branch in which the elimination takes place). The factors that cause these results are not completely understood, but the following conformational effects have been proposed as a partial explanation. The two anti- and two syn-periplanar conformations are, for a quaternary ammonium salt ... 

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