Solvent-induced chirality

An interesting phenomenon was observed when the CD of chiral molecules was measured in achiral solvents. The chiral solvent contributed as much as 10-20% to the CD intensity in some cases. Apparently, the chiral compound can induce a solvation structure that is chiral, even when the solvent molecules themselves are achiral. ... 

A few synthetic helical polymers are known to act as chiral selectors.7a,918d l8k i9d i9h ancj are widely used as chiral stationary phases (CSP) in gas or liquid chromatography.73,53 Recently, it has been reported that the preference of one helical sense in isotropic solution can be induced by some interaction between optically inactive polymers and chiral solvents/additives. Examples of this include poly(n-hexyl isocyanate)18d l8k and poly(phenylacetylene)s bearing functional group.19d 19h The polysilane derivatives also show chiral recognition ability in solution at room temperature. Poly(methyl-ft-pinanylsilane) includes two chiral centers per bulky hydrophobic pinanyl side group28 and... 

Preferential helical screw sense polysilanes with main-chain chirality are essentially of two types those in which PSS chirality is induced by an internal chiral field, for example, incorporation of enantiopure chiral (unichiral) side chains or end groups, and those which are inherently achiral, in which PSS chirality is induced by an external chiral field, such as a unichiral additive or solvent. 

Reductive metallation of aldehydes (but not ketones) by tri-n-butyl-(trimethyisilyl)stannane to yield a-hydroxystannanes is catalysed by tetra-n-butylammonium cyanide [15]. Other phase-transfer catalysts are not as effective and solvents, other than tetrahydrofuran, generally give poorer conversions. Use of a chiral catalyst induced 24% ee with 3-phenylpropanal. 

As was already mentioned, the phenomenon of nonequivalence of NMR spectra of enantiomers in chiral solvents is a basis for the determination of enantiomeric purity of a variety of chiral sulfur compounds. This method, developed by Pirkle, has the advantage over other methods of being absolute that is, the chemical shift difference between enantiotopic nuclei induced by the chiral solvent increases with increasing optical purity of the solvent, whereas the relative intensities of the signals that are used to measure the enantiomeric composition of the solute are not affected. 

It can be seen that the de does not reach zero, as the benzylic chiral center induces diastereoselective imine reduction, depending upon the system thermodynamics (that is catalyst, solvent, and temperature). Since the epimerization is first order with respect to the (IS, 4R) isomer but zero order with respect to the mixture of isomers, the process is unaffected by concentration and was conveniently run at the same high concentration as that of the mother liquors from the resolution process. A critical part of the process was the separation of the catalyst from the product, and its removal after the amine epimerization was preferred as this provided the greatest potential for its recycle. Removal of the catalyst was achieved by forming an insoluble ammonio complex formed by bubbling gaseous... 

We have investigated various factors which contribute to solvent-induced partial resolution or race-mization of 1,1 -binaphthyl (BN). Only photochemical interconversions of BN conducted in cholesteric mesophases influenced the steady state concentration of atropisomers. Thermal equilibriun in cholesteric media or photochemical interconver-sions in chiral isotropic solvents did not alter appreciably the atropisomeric ratio of initially racemic BN. Solvent order accelerates the rate of BN thermal racemization. A discussion of the physical properties of the solvents and BN responsible for the observations is presented. 

Chiral solvents rarely induce significant enantioselectivity, but ees up to 84% have been achieved in an aza-Baylis-Hillman reaction.161 Using an ionic liquid (IL), the anion of which is a dimalatoborate (54), it is suggested that the high enantioselectivity arises from strong ion-pair and hydrogen bond interactions with the zwitterionic intermediate of the reaction, i.e. IL-B- R3P+-CH2-CH=C(Me)-0 HO-IL. 

NMR shift differences between groups which are enantiotopic by external comparison (i.e. in enantiomers) may likewise be induced by either chiral solvents 26 27) or chiral shift reagents 52). Integration of the areas of signals of enantiomers so shifted is used for the determination of enantiomeric excess, a topic which cannot be taken up here but has been discussed elsewhere 53). 

It should be recalled that the calculation of solvent effects on optical activity presents some unique problems. A chiral solute induces a chiral structure of the surrounding solvent, even when the individual solvent molecules are achiral. This means that the solvent participates in the observed optical effect not only by a modification of the geometric structure and electronic density of the solute, but that part of the observed OR or circular dichroism arises from the chiral solvent shell rather than from the solute molecule as such. This is not accounted for by the PCM, and can be rendered only by an explicit quantum mechanical treatment of at least the first solvent shell, or preferably by molecular dynamics simulations. 

The circular dichroism induced in achiral compounds upon complexation with a chiral material can be used to characterize the nature of the interaction responsible for the association. Studies of this type may be conveniently classified as being the optical activity induced upon dissolution of a solute in a chiral solvent, through association of the species of interest with a co-dissolved chiral solute, or through association of the solute with chiral polymers. 

Optical Activity Induced Upon Dissolution of an Achiral Solute in a Chiral Solvent... 

In subsequent work, the CD induced in the n-ur transition of benzophenone was confirmed and studied in a variety of chiral solvent systems [4]. Representative examples of the CD induced by chiral several solvents in the benzophenone n- w band system are shown in Figure 1. In the same study, CD... 

A variety of studies have been performed in which the chirality induced in ketone chromophores has been characterized by CD spectroscopy. CD has been induced in the n-+ r transition of cyclohexanone upon its dissolution into several alcoholic and ester-functionalized solvent systems [5]. In this work it was established that hydrogen bonding between solute and solvent was not required for the generation of solvent-induced CD. In a more comprehensive work, the CD induced in 20 compounds containing a ketone chromophore was studied in approximately 15 chiral solvent systems [6]. It proved difficult to develop general rules for the observation (or lack thereof) of solvent-induced CD, with the rotational strengths being found to be solvent, temperature, and... 

However, the largest number of studies performed where chirality is induced upon dissolution of two solutes in a solvent system concerns the particular instance where the chiral solute is one of the cyclodextrins. These compounds are torus shaped, cyclic oligosaccharides consisting of six (denoted as a-cyclodextrin), seven (B-cyclodextrin), or eight (y-cyclodextrin) glucose units. Owing to their hydrophobic... 

Wamke I, Ay S, Brase S, Furche F (2009) Chiral cooperativity and solvent-induced tautom-erism effects in electronic circular dichroism spectra of [2.2]paracyclophane ketimines. J Phys Chem A 113 6987-6993... 

These studies show that the H-bonding network structures depend strongly on the nature of the chiral solute. The solvent induced chirality signatures provide significantly more detailed information about the explicit interactions between water and... 

In summary, chiral solvents have only induced limited enantioselectivity into different types of photochemical reactions as pinacolization, cyclization, and isomerization reactions. These studies are nevertheless very important, because they are among the early examples of chiral induction by an asymmetric environ ment. Based on our classification of chiral solvents as chiral inductors that only act as passive reaction matrices, effective asymmetric induction by this means seems to be intrinsically difficult. From the observed enantioselectivities it can be postulated that defined interactions with the prochiral substrate during the conversion to the product are a prerequisite for effective template induced enantioselectivity. 

Structurally symmetric achiral compounds may show optical activity in the presence of chiral solvent molecules owing to asymmetry induced by the chiral solvent. For example, the achiral carbonyl compounds benzil and benzophenone surprisingly show optical activity in the region of the n absorption in the CD spectrum when dis-... 

Figure 4.12 The structure of (a) [Pr4 (+)-(10) 9( X3-OH)](ClO4)2 and (b) [Pr3 (+)-(10) (1x3-0H)(H20)3] (C104)2 [18b]. (Reproduced with permission from O. Mamula, M. Lama, H.S. Evans and S. Shova, Switchable chiral architectures containing Prill ions an example of solvent-induced adaptive behavior, Angewandte Chemie International Edition, 2006, 45, 4940. Wiley-VCH Verlag GmbH Co. KgaA.)...

An excess helicity is induced by the effect of a chiral solvent or additive.41161171172 In the case of poly(hexyl isocyanate), a CD spectrum based on an excess helicity was observed in chiral chloroalkane solvents (Figure 10), and the sign and intensity of the CD... 

Finally, TSOSs can also be used directly as solvents, and applications of those for which the appended entity has a chemical effect on the outcome of the reaction will be explained in more detail during the next sections. On the other hand, some are used as sole solvent and have no effects besides traditional solvent effects. This is the case of chiral ionic liquids (CILs) which have been used extensively as chiral solvents in the hope of transferring the chiral information to the reaction product. CILs could eventually be seen as TSILs where the task would be to induce chirality, despite some promising results, detailing all their features would unnecessarily lengthen this review as other authors skillfully already did [42, 43],... 

Disubstituted phenols such as 350 undergo PhI(OAc)2-mediated oxidation in the presence of MeOH as a nucleophile resulting in the formation of two possible cyclohexa-dienones (351 and 352) (Scheme 73). The initially formed intermediate 353 is converted to the cyclohexadienones by two plausible routes. In route A, heterolytic dissociation generates a solvated phenoxonium ion 354, which further reacts with MeOH to afford 351 and/or 352. In route B, both 351 and 352 are produced by direct attack of MeOH on the intermediate (353). In the latter case, the reaction will be strongly influenced by steric factors and a homochiral environment using chiral solvents and chiral oxidants to induce some asymmetric induction, particularly in the formation of 352. 

Columnar stacks of 3,4,5-trialkoxy-benzoylated 3,3 -diamino-2,2 -bipyridine triamide derivatives of benzene-1,3,5-carboxylic acid (87, 88) have recently been studied in dilute alkane (dodecane) and chloroform solution (Chart 14). In chloroform, neither the derivative with hexyloxy tails (88) nor the one with chiral citronellol tails (87) showed Cotton effects in the CD spectrum. TTie chiral derivative 87 showed such effects in dodecane, whereas the achiral derivative 88 showed them in the chiral solvent, (/7)-2,6-dimethyloctane. Interestingly, addition of a small amount (2.5%) of chiral 87 to stacks of achiral 88 in hexane induced a strong Cotton effect, similar in magnitude to that of the pure chiral derivative in hexane. This is an example of the sergeant and soldiers effect in a noncovalent assembly, and it is similar to the effects already established for stiff helical polymers like polyiso-... 

In the remainder of this paper the solvent-dependent CD of a particular complex will be considered in some detail. The example has been chosen because the variation in CD with solvent is related to a solvent-induced change in the conformer populations of a chiral ligand. 

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