Asymmetric Autocatalysis---Discovery and Development---

Kenso SOAI*, Takanori SHIBATA† and Itaru SATO

Department of Applied Chemistry, Faculty of Science, Science University of Tokyo; Kagurazaka, Shinjuku-ku, Tokyo 162-8601 Japan
† Present address: Department of Chemistry, Faculty of Science, Okayama University; Tsushima, Okayama-shi 700-8530 Japan

The asymmetric autocatalysis is an enantioselective synthesis where the asymmetric catalyst and the product possess the same structure and the same absolute configuration. We disclosed chiral α-isopropyl-3-pyridinemethanols, α-isopropyl-5-pyrimidinemethanols, and α-isopropyl-3-quinolinemethanols operate as asymmetric autocatalysts in the enantioselective additions of i-Pr2Zn to 3-pyridinecarbaldehyde, 5-pyrimidinecarbaldehyde and 3-quinolinecarbaldehyde, respectively. Especially, practically perfect asymmetric autocatalysis (>99% yield and >99.5%e.e.) is attained by using 2-(3,3-dimethyl-1-butynyl)-α-isopropyl-5-pyrimidinemethanol as an asymmetric autocatalyst. Moreover, consecutive asymmetric autocatalytic reaction enables α-isopropyl-5-pyrimidine- and α-isopropyl-3-quinolinemethanols as well as 5-(1-hydroxy-2-methylpropyl)pyridine-3-carboxamides with extremely low e.e. to automultiply with dramatic amplification of e.e. without any assistance of other chiral auxiliaries.
It was also found that various chiral compounds can operate as chiral initiators in the enantioselective addition ofi-Pr2Zn to 5-pyrimidinecarbaldehydes and α-isopropyl-5-pyrimidinemethanols with high e.e. were obtained. For example, in the presence of L-leucine with 2 %e.e., asymmetric autocatalysis affords an (R)-α-isopropyl-5-pyrimidinemethanol with high e.e. It is known that asymmetric degradation of racemic leucine using circularly polarized light (CPL) gives chiral leucine (ca. 2 %e.e.). Thus, asymmetric autocatalysis with amplification of e.e. serves as a correlation between CPL and highly enantiomerically enriched organic molecules. Moreover, enantiomorphic inorganic crystals such as quartz (SiO2) and sodium chlorate (NaClO3) can be utilized as chiral initiators and an α-isopropyl-5-pyrimidinemethanols with high e.e. was obtained in high yields.


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