不斉触媒および反応場の設計に基づく高エナンチオ選択的不斉合成反応の研究

Abstract

Highly enantioselective asymmetric syntheses, i.e., enantioselective addition of alkylmetal reagents to aldehydes and imines, enantioselective conjugate addition of dialkylzincs to enones, and asymmetric autocatalysis have been developed by designing asymmetric catalysts (or chiral ligands) and chiral environment of the reactions. Automultiplication of chiral compounds by asymmetric autocatalysis was discovered where a chiral product acts as a chiral catalyst for its own production. Asymmetric autocatalysis with>99.5% ee in a yield of > 99% was attained using pyrimidyl alkanol as an asymmetric autocatalyst in the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde. The asymmetric autocatalysis exhibits significant positive non-linear effect on ee. Asymmetric autocatalyst with very low (ca. 0.00005%) ee enhances its ee significantly up to > 99.5% ee during the consecutive asymmetric autocatalysis without the assistance of any other chiral auxiliary. Moreover, amino acids and [6] helicene with very low ee which are produced by asymmetric photolysis and photosynthesis using circularly polarized light serve as chiral initiators of asymmetric autocatalysis, and pyrimidyl alkanol with high ee is obtained. Inorganic chiral crystals such as quartz and sodium chlorate, [2.2] paracyclophanes, allenes, chiral cobalt complexes due to the topology of coordination, chiral primary alcohols due to the deuterium substitution also work as chiral initiators. Asymmetric autocatalysis is capable to discriminate efficiently the chirality of various chiral compounds. Moreover, the reactions of pyrimidinecarbaldehyde with diisopropylzinc without adding chiral substance exhibit the formation of enantioenriched S or R pyrimidyl alkanols with approximate stochastic distribution, which indicates the reaction is a spontaneous absolute asymmetric synthesis. These results correlate for the first time the proposed origins of chirality of organic compounds with the chirality of organic compounds with very high ee.