Separation of the meso and racemic isomers

To 500 mL of methanol in a 2-L beaker is added 100 g (0,21 mole) of 5,7,7,12,14,14-Me6[14]4,ll-diene-l,4,8,ll-N4-2HC104 [Sec. 1-B]. The solution is stirred and 19 g (0.63 mole) of sodium tetrahydroborate(l-) and 16.5 g (0.42 mole) of sodium hydroxide are added in alternate small portions over a 1-hour period. The addition should be conducted in a well-ventilated fume hood (hydrogen is evolved) and in a cold-water bath to moderate the temperature, if necessary. After the addition is complete, the solution is stirred for 1 hour at room temperature and then heated to reflux for 15 minutes. After it is cooled, 50 g of sodium hydroxide in 1 L of water is added and the solution is stirred until precipitation of the product is complete (usually about 1 hr) and then filtered. The white product is washed with cold water and air-dried overnight. Additional material can be recovered from the filtrate by volume reduction. The yield is 52 g (88%). The product is a 50 50 mixture of the meso and racemic isomers that can be separated by fractional crystallization from methanol as detailed below. ... 

The rac-isomers have a twofold axis and therefore C2-symmetry. The meso-isomer has a mirror plane as the symmetry element and therefore Cs-symmetry. For polymerisation reactions the racemic mixture can be used since the two chains produced by the two enantiomers are identical when begin- and end-groups are not considered. Note When catalysts of this type are to be used for asymmetric synthesis, e.g. as Lewis acids in Diels-Alder reactions, separation of the enantiomers is a prerequisite [25],... 

By chromatography on A1203 the racemic mixture and the meso form could be separated. The racemic form melted at about 320°, resolidified and melted again at the melting point of the meso form 35,37). From the other double helicenes only one isomer could be isolated. 

Complexes of unsymmetrically substituted conjugated dienes are chiral. Racemic planar chiral complexes are separated into their enantiomers 84 and 85 by chiral HPLC on commercially available /f-cyclodextrin columns and used for enantioseletive synthesis [25]. Kinetic resolution was observed during the reaction of the meso-type complex 86 with the optically pure allylboronate 87 [26], The (2R) isomer reacted much faster with 87 to give the diastereomer 88 with 98% ee. The complex 88 was converted to 89 by the reaction of meldrum acid. Stereoselective Michael addition of vinylmagnesium bromide to 89 from the opposite side of the coordinated Fe afforded 90, which was converted to 91 by acetylation of the 8-OH group and displacement with EtjAl. Finally, asymmetric synthesis of the partial structure 92 of ikarugamycin was achieved [27],... 

Among the more widely studied 2,3-C-disubstituted ligands related to ethylenediamine are sbn and stien (Table 3). These ligands can exist in meso and racemo forms and the properties e.g. solubility) of transition metal complexes (especially Co" ) with the two forms of this type of ligand are often sufficiently different as to allow amine isomer separation to be achieved without separation of the amine mixture. Meso and racemic 5bn are prepared together by the reduction of dimethyl-glyoxime and can be separated by fractional crystallization of the dihydrochloride salts. There are, however, stereospecific synthetic routes available for the meso and racemo forms of stien (Table 6). 

For the synthesis of the meso forms [(RRSS) and (RSSR)] as well as the racemates of 111, 112 and 113, the racemic C 15-alcohol 114 was benzoylated, treated with the Lewis acid BF3 etherate and saponified to give a mixture of the stereoisomers of 115. After oxidation, the (cis)- and (trans)-isomers 116 and 117 of the Cis-aldehyde were separated (Scheme 26). 

It must be kept in mind that the ( )-diastereomer is a mixture of enantiomers that were not separable by reverse phase HPLC. Since the method for separation of (+)- and meso-diastereomers (reverse phase HPLC, C-18 column) is based on the difference in conformation between isomers (related ultimately to their differential attraction to the column), it is unlikely that the two enantiomers of the (+ )-diastereomer have different conformations at the air-water interface. It is not known, however, how the energetics of compression and expansion will differ for films cast from either R,R or S,S enantiomer from those cast from the racemic mixture. 

The coordination chemistry of macrocyclic ligands has been extensively studied and aspects of isomerism have been considered in numerous systems.241 Methods whereby two diastereomers of complexes of tetra- N-methylcyclam may be isolated have been discussed previously.184 This, however, is a relatively simple system and it is usually necessary to consider isomerism due to the presence of asymmetric atoms in the chelate arms, as well as that due to asymmetric donor atoms that may be rendered stable to inversion by coordination. An example of a system exhibiting this level of complexity is afforded by the nickel(II) complexes of the macrocyclic ligands generated by reduction of the readily prepared macrocycle (46). These ligands contain two asymmetric carbon atoms and four asymmetric nitrogen atoms but, because AT-inversion is rapid, it is conventional to consider that only three separable stereoisomers exist. There is an enantiomeric pair, (47a) and (47b), which constitutes the racemic isomer (R, R ), and an achiral (R, S ) diastereomer (47c), the meso isomer. 

The transformation of tetrasubstituted ethylenes into 1,2,4-trioxolanes may also be achieved if the ozonolysis is carried out in the presence of a foreign carbonyl compound as described in Section 4.33.3.4. With formaldehyde as added carbonyl compound, 3,3-disubstituted derivatives are obtained, whereas in the presence of excess ketone (e.g. by using the latter as solvent), the ozonolysis gives rise to tetrasubstituted 1,2,4-trioxolanes which are difficult to prepare by other methods. Reactions (163) -> (164) and (165) -> (166) provide two examples of this versatile 1,2,4-trioxolane synthesis. Unlike the parent system (2), alkyl- and/or aryl-substituted 1,2,4-trioxolanes generally are stable, non-explosive compounds. Mixtures of crossed ozonides (cf. Section 4.33.3.1.1) or of cis and trans isomers can be separated by thin layer, column or gas chromatography. The cis isomers of symmetrical 3,5-disubstituted 1,2,4-trioxolanes are meso forms, whereas the corresponding trans isomers represent racemates which in some cases have been resolved into their optical... 

Under the current reaction conditions, H-NMR reaction monitoring indicated that a 4 1 isomeric product ratio of pseudo-rac and meso dimethylsilanediylbis(2-methyl-4,5-benzo-indenyl)zirconium monochloride mono(2,4-di-t-butylphenoxide), (I), and (II), respectively, were formed. The isomers were separated by extracting the racemic mixture with hot toluene. 

Thus from a study of the crystalline sodium-ammonium salt of racemic acid and of dextro tartaric acid Pasteur showed, conclusively, the relationship of these two acids to each other and also discovered the existence of a third isomer optically active but of opposite direction to the ordinary tartaric acid already known. Racemic acid, therefore, is optically inactive because it consists of equal molecules of the ordinary dextro tartaric acid and the newly discovered levo tartaric acid. Also racemic acid can be resolved into its optically isomeric components by mechanically separating the two forms of crystals of the sodium-ammonium salt. The two active forms of tartaric acid, when mixed in equal molecular amounts, yield the inactive or racemic acid. Later, Pasteur prepared the fourth variety of tartaric acid, viz., meso-tartaric acid, by heating the cinchonine salt of dextro tartaric acid. This new acid proved to be inactive like racemic acid, but, unlike it, was unable to be resolved into optically active components. Its relation to the other three forms of tartaric acid was unexplained by Pasteur. 

Diamine 263 is made by the radical (pinacol style) dimerisation of the benzaldehyde imine 268. This gives a diastereomeric mixture equilibrated in favour of the syn isomer with lithium in isoprene and separated (51% yield) from the meso isomer by crystallisation with racemic tartaric acid.47 Finally, ( )-263 is resolved with a single enantiomer of tartaric acid giving 90% yield of either (S,S)-263 or (R,R)-263, depending on which enantiomer of tartaric acid is used, in 99% ee. The isomer remaining in solution can be isolated with only slightly worse ee 96%. 

Resolution by transesterification. Using vinylic acetates to esterify allyl alcohols, propargyl alcohols, 2-phenylthiocycloalkanols, a-hydroxy esters," methyl 5-hydroxy-2-hexenoates, and 2-substituted 1,3-propanediols, the enantioselective esterification provides a means of separation of optical isomers. Vinyl carbonates are also resolved by lipase-mediated enantioselective conversion to benzyl carbonates. Other esters that have also been used in the kinetic resolution include 2,2,2-tri-fluoroethyl propionate. There is a report on a double enantioselective transesterification" of racemic trifluoroethyl esters and cyclic meso-diols by lipase catalysis. 

A detailed investigation of the stereochemistry of cis- and tran5-[RuCl2(L-L)2] (l L = o-QH< (EMePh)2 E = As, P) has been undertaken. The optically active, racemic, meso, syn, and anti forms of the trans compound were isolated for both ligands each of these subsequently isomerized to the corresponding cis complex by reaction with AlEts and the various diastereoisomers of the latter separated and characterized. Whereas the trans isomers are relatively inert, the cis complexes readily undergo stereospecific halogen substitution by 1 and A minor product obtained... 

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