Enantiomeric chiral seed crystal

Scheme 3.3-3 Enantiomeric separation of 10a by inciusion com-piexation with 111 in the presence of chiral seed crystals.

So we can generate chiral material from racemic or achiral material quite easily. It s just that we couldn t predict ahead of time which one we might get— that is, unless you have an external chiral influence We discussed this general idea when we described the chiral photodestruction of molecules in interstellar space. The chiral force here is the circularly polarized light that is expected to preferentially destroy one enantiomer more rapidly than the other. Chemists know that if you have a saturated solution that is cooling down and ready to crystallize, you can influence which crystal you get from the two racemic possibilities by "seeding" the solution with a chiral seed crystal. This will often initiate the formation of the desired enantiomeric crystal, and then the autocatalysis takes over and more of these enantiomeric crystals are formed. 

The achiral inorganic ionic sodium chlorate (NaClOs) and sodium bro-mate (NaBrOs) crystallize in enantiomeric forms belonging to the P2i3 space group for which the same crystal structures exhibit opposite optical rotation [89]. The levo-(Z) and dextrorotatory (d) crystals can be obtained in equal proportions [90]. The chiral ionic crystals of NaClOs and NaBrC>3 were subjected to asymmetric autocatalysis as the initial seed of chirality to study the correlation between the organic compound with high ee and the chiral inorganic crystal composed of achiral ionic components. 

When pyrimidine-5-carbaldehyde 11 was treated with z-Pr2Zn in the presence of powdered [CD(+)260]-crystal, (S)-pyrimidyl alkanol with 73% ee was obtained in 88% yield (Scheme 16). On the other hand, in the presence of [CD(-)260]-crystal, the opposite enantiomer (R)-12 with 89% ee was isolated in 89% yield. When the crystals, grown from the stirred methanol solution of hippuric acid using each enantiomorph of hippuric acid as the seed crystal, were used in asymmetric autocatalysis, the same correlation between the chirality of crystal and the product 12 was observed with excellent reproducibility. It should be noted that nearly enantiopure (S)- and (K)-pyrimidyl alkanols 12 with > 99.5% ee were obtained by consecutive asymmetric autocatalysis [64], In this system, after the enantiomorphs of the crystal induced the chirality of an external organic compound, the subsequent asymmetric autocatalysis gave a greater amount of enantiomerically amplified product. 

Since the crystal of pip-1 is chiral, it should be either of the two enantiomer crystals D and L. The absolute structures of 20 crystals obtained from a soluti containing racemic compounds indicated that 12 crystals are D and 8 are L. Wh seed crystals with one of the enantiomeric structures, D or L, were added to racemic solution, all the crystals showed the same enantiomeric structures as of the seed crystals. The enantiomeric D L ratio of 20 crystals became 20 0. 

The powdered sample with the same enantiomeric structures, D or L, w irradiated with a xenon lamp for 20 h and was dissolved in a chloroform solutio The specific rotation [a]D of the chloroform solution was 4 30°. It is clear th the racemic-to-chiral transformation can be observed only by photoirradiatio Using the seed crystals, one of the enantiomeric crystals was selected in ea experiment. This means that the A molecules have R configurations in the pi 1 to pip-5 crystals. 

The first method of enantiomeric separation by direct crystallization is the mechanical technique use by Pasteur, where he separated the enan-tiomorphic crystals that were simultaneously formed while the residual mother liquor remained racemic. Enantiomer separation by this particular method can be extremely time consuming, and not possible to perform unless the crystals form with recognizable chiral features (such as well-defined hemihedral faces). Nevertheless, this procedure can be a useful means to obtain the first seed crystals required for a scale-up of a direct crystallization resolution process. When a particular system has been shown to be a conglomerate, and the crystals are not sufficiently distinct so as to be separated, polarimetry or circular dichroism spectroscopy can often be used to establish the chirality of the enantiomeric solids. 

The reaction can be initiated by a diversity of small chiral seeds including chiral crystals of achiral compounds such as quartz [175] and adenine [176]. Recently, it was found that even isotopomers are effective [177,178]. An amino acid with the level of enrichment derivable from CPL irradiation was found to be an effective seed [179], as was the CPL-irradiated reaction product itself [180], providing a model for a reaction that can be amplified from the kinds of enantiomeric imbalances found in Nature. 

Resolution of a racemic mixture was discovered by Pasteur in the last century. It remains an useful method to prepare enantiomerically pure compounds, although the yield in the desired enantiomw cannot exceed 50%. It is realized by the reaction of stoichiometric amounts of a chiral auxiliary which will produce a I I mixture of diastereomers, generally easy to separate. Removal of the chiral auxiliary graerates the desired enantiomer. A special case of resolution is one in which the racemic compound crystallizes as a conglomerate. Here, a chiral seed can propagate the production of... 

X-Ray crystallographic analysis revealed that the crystal of thioamide 39 was chiral and the space group was P2i2 2. The absolute configuration of (-)-rotatory crystals of 39 was determined by the X-ray anomalous scattering method as (-)-(M)-39 for the helicity. The (-)-rotatory crystals obtained by the seeding method were irradiated at 0°C until the reaction conversion reached 100 % yield. As expected, the asymmetric induction in 40 was observed in 10% ee. By suppression of the reaction conversion to 30% and decrease of the reaction temperature to -45°C, the enantiomeric purity rose up to 40% ee. 

The chiral crystals were spontaneously obtained from the solutions of 1 and 2,4-dichlorobenzylamine 3 (Scheme 27.1b). This kind of chiral crystallization of achiral molecules leads neccessarily to left- and right-handed crystals. The enantiomeric crystals of M- and P-1-3 were selectively prepared by seeding. Irradiation of the crystals of M-l-3 at around 350 nm through a UV filter gave a cyclopentenol (R,R)-5 as almost the sole product, achieving absolute asymmetric photocyclization [25]. In contrast, irradiation at >290 nm afforded (R,R)-5, (P)-4, and (P)-hydrol in a 6 3 1 molar ratio the enantiomeric excesses of the three products were higher than... 

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