Enantiomers diastereomeric crystallisation

Initially, studies on the preparation of the borate complexes of the type 3 using bi-2-naphthol, S-proline and B(OH)3 were carried out. These experiments revealed that the bi-2-naphthol and S-proline form a 2 1 diastereomeric inclusion complex in the absence of boric acid (Scheme l).5 Unfortunately, efforts to improve the optical purity through crystallisation did not yield fruitful results. However, both the enantiomers can be obtained in pure forms by carrying out the experiments again using the partially resolved samples.5... 

The triazole fungicides of general structure 64 such as hexaconazole 65 and flutriafol 66 are a rare case of human and plant medicine using similar compounds. They were initially used as racemates but it was soon essential to discover the active enantiomers. Conventional resolution by crystallisation of diastereomeric derivatives proved difficult. 

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%. 

Even for industrial-scale production of optically active amino acids, classical crystallisation technologies may offer an appropriate alternative to enzymatic methods. Either the seeding with one of the enantiomers (e.g. from S-(carboxy-methyl)-(L)-cysteine), or the crystallisation of diastereomeric salts with bases like derivatives of ephedrine or phenylethylamine maybe suitable (Fig. 4.16). 

While compounds which are enantiomers have identical chemical and physical properties and equal and opposite optical rotation, compounds which are diastereomeric with each other can have completely different chemical and physical properties and optical rotations. This feature provides the basis for the resolution of chiral compounds. In this procedure a racemic mixture is derivatised by reaction with an enantiomerically pure compound which leads to a mixture of two diastereomers. These can be separated by crystallisation or chromatography as a result of their different properties and the pure enantiomers of the starting compound obtained by cleavage of each diastereomer separately. In the synthesis of the chiral phosphines (section 1.7) the phosphine oxide (37) is obtained by resolution of the starting material (34) via the diastereomeric esters (35) and (36). A further important application of the differing properties of diastereomers is in the determination of e.e. by derivatisation with an enantiomerically pure compound followed by chromatographic or NMR analysis (see section 3.4.1). 

Resolution may be considered the classical method of obtaining enantiomerically pure products. The procedure relies on the fact that diastereomers, unlike enantiomers, have different physical properties. If the racemic compound which is to be resolved is derivatised by reaction with a naturally occurring enantiomerically pure compound, then the resulting diastereomeric compounds may be separated, most commonly by crystallisation but also by chromatography, and then separately treated to liberate the two enantiomers. If we represent the... 

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