Contents Members ŋ߂̌ Pubulications
Recent Research (Originals) (Reviews)
Recent Research (Page 1) Page 2
(1) Asymmetric autocatalysis (Asymmetric automultiplication, Self-replication of chiral compounds)
Asymmetric autocatalysis is a reaction in which chiral product acts as a chiral catalyst for its own production. The process is an automultiplication of chiral compounds without the assistance of any other chiral compound than itself. Asymmetric autocatalysis has advantages over conventional asymmetric catalysis.
i) The efficiency is very high because the amount of catalyst increases during the reaction.
ii) The product has the same structure as that of catalyst and can be used as an asymmetric autocatalyst for the next run. Thus, the factor of multiplication of compound is infinite by consecutive asymmetric autocatalysis.
iii) No need for the separation of product from the catalyst.
We found the first examples of asymmetric autocatalysis. Chiral pyrimidyl alkanols, quinolyl alkanols, pyridyl alkanols act as asymmetric autocatalyes in the enantioselective addition of dialkylzinc, especially diisopropylzinc, to pyrimidinecarbaldehyde, quinolinecarbaldehyde and pyridinecarbaldehyde to afford themselves with high enantiomeric excesses (ee). Among them, 2-alkynylpyrimidiyl alkanol automultiplies in the reaction of 2-alkynykpyrimidine-5-carbaldehyde and diisopropylzinc with greater than 99.5% ee in greater than 99% yield.
(2) Asymmetric autocatalysis with amplification of enantiomeric excess
It was found that enantiomeric excess of asymmetric autocatalyst enhances during the reaction. (S)-Pyrimidyl alkanol with as low as ca. 0.00005% ee, i.e., ratio of S and R enantiomers is ca. 50.000025 : 49.999975, enhanced its ee to greater than 99.5% ee after three consecutive asymmetric autocatalyses with the automultiplication of the amount by a factor of 630,000 times. On the other hand, (R)-pyrimidyl alkanol with ca. 0.00005% ee afforded (R)-pyrimidyl alkanol with greater than 99.5% ee. These results show that asymmetric autocatalysis with amplification of enantiomeric excess enables a chiral compound with tiny enantiomeric imbalance to become highly enantiomerically enriched without the assistance of any other chiral auxiliary.
(3) Origins of chirality, origins of chirality of biomolecules
The origins of homochirality of biomolecules such as L-amino acids and D-sugars have been an intriguing puzzle for many years. How was the enantiomerically enriched organic compound initially formed? Several mechanisms of the origin of chirality have been proposed such as circularly polarized light (CPL) and quartz. However, the enantiomeric imbalances induced by these mechanisms have been extremely low. The chemical process, i.e., link, leading to very high enantiomeric excess of biomolecules has been missing.
We found that asymmetric synthesis promoted by d- and l-quartz in conjunction with asymmetric autocatalysis affords (S) and (R)-pyrimidyl alkanol, respectively, with very high enantiomeric excess. Thus, the chirality of inorganic crystal and that of an organic compound with high enantiomeric excess has been successfully correlated. Leucine and hexahelicene with less than 2% ee, which are induced by CPL, work as chiral initiators of asymmetric autocatalysis to afford pyrimidyl alkanol with high ee. Thus chirality of CPL and that of an organic compound has been correlated for the first time.
Asymmetric autocatalysis works in chiral recognition and chiral differentiation. The reaction of pyrimidinecarbaldehyde and diisopropylzinc in the presence of 2 mol% of (S)-2-butanol with 0.1% ee affords (R)-pyrimidyl alkanol with high ee, while (R)-2-butanol with 0.1% ee affords (S)-pyrimidyl alkanol. The results show that the chirality of 2-butanol with low ee is distinguished by asymmetric autocatalysis. Other compounds such as chiral alpha deuterated benzyl alcohol, mono substituted [2.2]pracyclophane, 1, 3-disubstituted allene, chiral Co complex due to the topology of ligand serve as chiral initiators of asymmetric autocatalysis.
Asymmetric autocatalysis without using any chiral auxiliary affords enantiomerically enriched pyrimidyl alkanol. The initial fluctuations of the ratio of enantiomers is enhanced by asymmetric autocatalysis with amplification of enantiomeric excess. The results show that the reaction is spontaneous (absolute) asymmetric synthesis.
(4) Dendritic chiral catalyst
We developed dendritic chiral catalysts. The dendrimer with chiral moiety at terminals work as highly enantioselective chiral catalysts and ligands for the addition of dialkylzincs to aldehydes and phosphinyl imines.
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