Asymmetric autocatalysis - Discovery and development

The asymmetric autocatalysis is an enantioselective synthesis where the asy mmetric catalyst and the product possess the same structure and the same ab solute configuration. We disclosed chiral alpha -isopropyl-3-pyridinemethan ols, alpha -isopropyl-5-pyrimidinemethanols, and alpha -isopropyl-3-quino- linemethanols operate as asymmetric autocatalysts in the enantioselective a dditions of i-Pr2Zn to 3-pyridinecarbaldehyde, 5-pyrimidinecarbaldehyde and 3-quinolinecarbaldehyde, respectively. Especially, practically perfect asy mmetric autocatalysis ( > 99% yield and > 99.5%e.e.) is attained by using 2 - (3,3-dimethyl-1-butynyl)-alpha -isopropyl-5-pyrimidinemethanol as an asym metric autocatalyst. Moreover, consecutive asymmetric autocatalytic reactio n enables alpha -isopropyl-5-primidine- and alpha -isopropyl-3-quinolinemet hanols as well as 5-(1-hydroxy-2-methylpropyl) pyridine-3-carboxamides with extremely low e.e. to automultiply with dramatic amplification of e.e. wit hout any assistance of other chiral auxiliaries. It was also found that various chiral compounds can operate as chiral initi ators in the enantioselective addition of i-Pr2Zn to 5-pyrimidinecarbaldehy des and alpha -isopropyl-5-pyrimidinemethanols with high e.e. were obtained . For example, in the presence of L-leucine with 2 %e.e., asymmetric autoca talysis affords an (R)-alpha -isopropyl-5-pyrimidinemethanol with high e.e. It is known that asymmetric degradation of racemic leucine using circularl y polarized light (CPL) gives chiral leucine (ca. 2 %e.e.). Thus, asymmetri c autocatalysis with amplification of e.e. serves as a correlation between CPL and highly enantiomerically enriched organic molecules. Moreover, enant iomorphic inorganic crystals such as quartz (SiO2) and sodium chlorate (NaC lO3) can be utilized as chiral initiators and an alpha -isopropyl-5-pyrimid inemethanols with high e.e. was obtained in high yields.