Cryptochirality

A second concept—that of cryptochirality-also illustrated by Mislow and... 

The difference in the ligands of each tertiary atom is due mainly to the different length of chain segments to which it is bonded. If we consider that, in the absence of cooperative factors, optical activity is a short-range phenomenon, the contribution to the rotatory power of most parts of the chain is zero or near to zero. One can thus foresee that the optical activity of a single enantiomer is very small and falls into the domain of cryptochirality. Only oligomers of low molecular weight can present measurable optical activity. 

A polymer sample with even a limited dispersion of molecular weight consists of a mixture of molecules of the first and of the second type and is, therefore, cryptochiral (262). 

With the third model, also, the single chains are chiral but with negligible optical activity. Even in this case we are in the cryptochirality domain, except possibly with low molecular weight compounds. 

It should be observed that the concept of cryptochirality according to Mislow and Bickart concerns the properties of a real sample while here it seems to be intrinsic to the model. 

There is an interesting theoretical report concluding that the polymerization giving an atactic polymer can be asymmetric synthesis polymerization without using chiral catalysts [95]. According to the report, when DP of an atactic polymer exceeds 70, the polymer sample cannot be a racemic mixture because the number of possible diastereomers is far larger than that of polymer chains and only one antipode of enantiomer can exist for some of the diastereomeric chains. However, the polymer sample does not show optical activity due to compensation of optical rotations contributed from different diastereomers (cryptochirality). 

Such enantiomerically pure chiral compounds, which are optically inactive in the generally investigated UV/Vis spectral range from 200 to 800 nm, can be designated as cryptochiraF according to Mislow et al., since the chiral information is hidden in the molecule (i.e. present in cryptic form) [12a, 20]. Cryptochirality of the dendrimer is explained on the one hand by the pronounced conformational mobility of the dendrimer branches and on the other by the slight electronic difference between the dendritic substituents. 

Discrimination of Cryptochirality in a Saturated Quaternary Hydrocarbon by Asymmetric Autocatalysis... 

An example of a compound whose chiral discrimination poses the utmost difficulty is a saturated quaternary hydrocarbon bearing similar substituents on the asymmetric carbon atom, with a representative example being 5-ethyl-5-propylundecane,i.e., (n-butyl)ethyl(n-hexyl)(n-propyl)methane (Fig. 8) [ 106]. The enantiomer of this hydrocarbon exhibits practically no optical rotation ( of < 0.001) between 280 and 580 nm. The compound is a chiral, but to all intents an optically inactive, compound. To the best of our knowledge, the chirality of this compound has not been discriminated using any current method. Mislow called such hidden chirality cryptochirality [ 14,107]. 

Scheme 20 Chiral discrimination of cryptochiral quaternary hydrocarbon...

It was shown that the asymmetric autocatalysis of chiral pyrimidyl alkanol is the only possible method to discriminate cryptochiral quaternary saturated hydrocarbons, whose chirality is not capable of determination by any current... 

The model with different end-groups is not realistic in all cases isotactic polypropylene and syndiotactic polypropylene are chiral, or more precisely, their structure is cryptochiral. This model is to be chosen when examining oligomers, and especially when studying the polymerisation mechanism where the structure of the reactive chain end is of extreme importance [16]. 

As the preceding discussion suggests, conditions may exist under which even the most powerful measuring device available will be incapable of detecting a significant difference between samples of different enantiomeric composition above the noise level of stochastic achirality. We call such a system cryptochiral, because the model demands an excess of one enantiomer over the other in the time domain of observation, while the chirality phenomenon to be observed falls below the threshold of the operational null and thus is undetectable. Note that a cryptochiral substance is operationally indistinguishable from a stochastically achiral one because, at and below the operational null, enantiomorphous systems can be neither differentiated from each other nor distinguished from achiral ones. 

Optical Activity. Optical activity is the most characteristic index of optical purity in cases where the chiral excipients are suspected to be enantiomerically impure. Chiral excipients with no observable optical activity are assumed to be in a 1 1 ratio of enantiomers (racemates). However, the measurement may be accidental due to the storage conditions (such as temperature and medium) in which the determination was done, which could lead to changes in optical activity [15]. In such cases, the sample is not considered racemic but is said to be cryptochiral [16]. 

Powder x-ray diffraction spectra could show distinct bands for enantiomers and corresponding racemates if the latter is a racemic compound. The nonracemic character was reported for cryptochiral samples of triglycerides and 1-lauro dipalmitin [38,39]. Natural triglycerides had little or no optical activity (cryptochiral) while the synthetic racemic triglycerides showed optical activity. This property could be further characterized by inducing piezoelectricity (creation of charges on opposite faces of crystals... 

There are some notable exceptions where racemic or achiral starting materials consequently give the same enantiomer [72], The origin of this is not clear, but sometimes the concept of cryptochirality is used as an explanation, that is, due to Ihc presence for a very lung time on earth of basically enantiopure living organisms our environment is chiral, but at concentrations loo low to measure [73]. 

Alcohol 43 (entry 31) is a starting material for the synthesis of (R)-(+)-[VCD( )984]-4-ethyl-4-methyloctane 51, a cryptochiral saturated hydrocarbon with a quaternary chirality center, as will be discussed in section 55.3.4 (see Figure 55.26). Enantiopure alcohol (l/ ,2/ )-(—)-43 was obtained by the CSDP acid method, and its AC was unambiguously determined by X-ray crystallography." However, the MaNP acid method is better than the CSDP acid method in this case because of more effective HPLC separation of diastereomeric esters (see the result in section 55.3.4). 

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