Asymmetric autocatalysis and the origin of chiral homogeneity in organic compounds

• Published in: Chemical record Vol. 1; no. 4; pp. 321 - 332
• Main Authors: Soai, Kenso, Sato, Itaru, Shibata, Takanori
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 2001
• Subjects: Aldehydes - chemistry; amplification; asymmetric autocatalysis; asymmetric synthesis; Catalysis; circularly polarized light; dialkylzinc; Feedback, Physiological; Models, Molecular; Molecular Mimicry; origin of chirality; Pyrimidines - chemistry; quartz; Stereoisomerism; Zinc - chemistry
• ISSN: 1527-8999; 1528-0691
• DOI: 10.1002/tcr.1017

The discovery and development of asymmetric autocatalysis, in which the structures of the chiral catalyst and the chiral product are the same, are described. Chiral 5‐pyrimidyl, 3‐quinolyl, and 5‐carbamoyl‐3‐pyridyl alkanols act as highly enantioselective asymmetric autocatalysts in the enantioselective addition of diisopropylzinc to the corresponding aldehydes, such as pyrimidine‐5‐carbaldehyde. 2‐Alkynyl‐5‐pyrimidyl alkanol with an enantiomeric excess (ee) of >99.5% automultiplies practically perfectly as an asymmetric autocatalyst in a yield of >99% and >99.5% ee. Asymmetric autocatalysis with an amplification of ee has thus been realized. Consecutive asymmetric autocatalysis starting with chiral 2‐alkynylpyrimidyl alkanol of only 0.6% ee amplifies its ee significantly, and yields itself as the product with >99.5% ee. The reaction of pyrimidine‐5‐carbaldehyde and diisopropylzinc in the presence of chiral initiators with low ee’s, such as secondary alcohol, amine, carboxylic acid, mono‐substituted [2.2]paracyclophane, and chiral primary alcohols due to deuterium substitution, regulates the absolute configuration of the resulting pyrimidyl alkanols, and the ee of the resulting pyrimidyl alkanol is much higher than that of the chiral initiator. Leucine and [6]helicene with very low ee’s, which are known to be induced by circularly polarized light (CPL), also serve as chiral initiators to produce pyrimidyl alkanol with higher ee’s. Overall, the process represents the first correlation between the chirality of CPL and an organic compound with very high ee. Chiral inorganic crystals, such as quartz and sodium chlorate, act as chiral inducers in the asymmetric autocatalysis of pyrimidyl alkanol. The process correlates for the first time ever the chirality of inorganic crystals with an organic compound with very high ee. © 2001 John Wiley & Sons, Inc. and The Japan Chemical Journal Forum Chem Rec 1:321–332, 2001