Inducers, enantioselective asymmetric autocatalysis

We investigated highly enantioselective asymmetric autocatalysis of a chiral compound induced by the isotopic enantiomer of a primary alcohol-a-d (Scheme 22) [118]. The correlation between the absolute configurations of the obtained pyrimidyl alkanol and the isotopic chiral compound is reproducible, thus the small isotope chirality can be recognized by asymmetric autocatalysis. 

Chiral organic-inorganic hybrid materials such as silsesquioxane and ephedrine immobilized on silica gel also act as chiral inducers of asymmetric autocatalysis (Scheme 24) [124-126]. Enantioselective addition of z-Pr2Zn... 

Scheme 23 Helical silica-induced highly enantioselective asymmetric autocatalysis of chiral pyrimidyl alkanol...

In these systems, after the crystal chirality induced the chirality of asymmetric carbon in external organic compound, the subsequent asymmetric autocatalysis gives the greater amount of enantiomerically amplified product. These results clearly demonstrate that the crystal chirality of achiral organic compound is responsible for the enantioselective addition of /-Pr2Zn to pyrimidine-5-carbalde-hyde Ic. 

When enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde 89 was examined, simple 2-butanol with low (ca 0.1%) induces a tiny chirality in the initially produced alkanol 81 and the value of the finally obtained alkanol becomes higher (73-76%) due to the asymmetric autocatalysis (Table 2). Note that the value can be further amplified by subsequent asymmetric autocatalysis, as described in the preceding section. Various chiral compounds have been proved to act as chiral initiators. 

We reasoned that chiral organic compounds with low ee induced by CPL can act as a chiral trigger in the enantioselective addition of z -Pr2Zn to pyrimidine-5-carbaldehyde, and that the subsequent asymmetric autocatalysis of pyrimidyl alkanol, formed in situ, amplifies its ee to produce highly enantioenriched pyrimidyl alkanol with an absolute configuration corresponding to that of the handedness of the CPL. 

The pyrimidyl alkanol 120 with up to 99% ee is formed with the absolute configuration corresponding to the helical chiraHty of the thiaheHcenes used as chiral inducers. The enantioselectivity observed in this asymmetric reaction may be explained taking into account the coordination of /PraZn to the sulfur atoms of the chiral thiahehcene to form a chiral active zinc species. Since these chiral species react with pyrimidine-5-caibaldehyde 119 in the initial stage of the reaction, a small ee is initially induced. Then, a subsequent asymmetric autocatalysis with an amplification of the ee affords the alkanol, as a zinc alkoxide, with a high ee, which shows the corresponding absolute configuration. 

This is the first example of a highly enantioselective reaction induced by chirality resulting from deuterium substitution of amino acids. In addition, chirally deuterated primary alcohols [52] and chiral amino acid derivatives with partially deuterated substituent such as monodeuterated methyl group (—CDH2) can induce the chirality in asymmetric autocatalysis [53]. 

Carbon-isotope chirality is experimentally difficult to discriminate because the chirality originates from the very small difference between the carbon-12 and carbon-13. Therefore, it has been a question whether isotopically substituted carbon chiral compounds can induce chirality in some enantioselective reactions. To address this problem, we performed asymmetric autocatalysis triggered by a chiral compound arising solely from carbon-isotope substitution. 

Kawasaki T, Ozawa H, Ito M, Soai K (2011) Enantioselective synthesis induced by compounds with chirality arising from partially deuterated methyl groups in conjunction with asymmetric autocatalysis. Chem Lett 40 320-321. doi 10.1246/cl.2011.320... 

Kawasaki, T., Ishikawa, K., Sekibata, H., Sato, 1., and Soai, K. (2004) Enantioselective synthesis induced by chiral organic-inorganic hybrid silsesquioxane in conjunction with asymmetric autocatalysis. Tetrahedron Lett, 45, 7939-7941. 

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