Hippuric acid asymmetric autocatalysis

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. 

Scheme 16 Asymmetric autocatalysis induced by a chiral crystal of hippuric acid...

Chiral organic crystals composed of achiral compounds such as hippuric acid act as the initial source of chirality of asymmetric autocatalysis to produce the highly enantiomerically pure product. In this reaction, chiral organic crystals are utilized as a chiral inducer, not as a reactant. Therefore, these results are the realization of the process in which the crystal chirality of achiral organic compounds induces asymmetry in another organic compound whose chirality was amplified to produce a large amount of enantiomerically pure organic compound, pyrimidyl alkanol in conjunction with asymmetric autocatalysis. 

In addition, the enantiomorphous crystals composed of achiral hippuric acid [42], benzil [43], and tetraphenylethylene [44] have been used successfully as chiral inducers in asymmetric autocatalysis. Chiral crystal of anhydrous cytosine formed from achiral monohydrate by the thermal dehydration [45] can also work as origin... 

Kawasaki T, Suzuki K, Hatase K, Otsuka M, Koshima H, Soai K (2006) Enantioselective synthesis mediated by chiral crystal of achiral hippuric acid in conjunction with asymmetric autocatalysis. Chem Commun 1869-1871. doi 10.1039/b602442d... 

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