Masateru Ito

Asymmetric autocatalysis triggered by carbon isotope (13C/12C) chirality.

The origin of chirality in asymmetric autocatalysis is due to carbon isotope substitution. Resolving Isotopically Chiral Alcohols Autocatalytic reactions, which are accelerated by their own product, can amplify small imbalances in the chiral distribution of starting materials. A particularly effective system is the alkylation of certain aldehydes by diisopropyl zinc, which becomes increasingly stereoselective as the chiral alkoxide product coordinates to unreacted zinc centers. Kawasaki et al. (p. 492, published online 26 March) show that the sense of enantioselection in this system can be influenced by a factor as subtle as chirality in an alcohol that arises only because two positions differ in having 12C and 13C atoms. Isotopically chiral ligands were carefully prepared by using methods that would avoid chiral contaminants, and each led to a distinct enantiomer with enantiomeric excesses exceeding 90%. Many apparently achiral organic molecules on Earth may be chiral because of random substitution of the 1.11% naturally abundant 13C for 12C in an enantiotopic moiety within the structure. However, chirality from this source is experimentally difficult to discern because of the very small difference between 13C and 12C. We have demonstrated that this small difference can be amplified to an easily seen experimental outcome using asymmetric autocatalysis. In the reaction between pyrimidine-5-carbaldehyde and diisopropylzinc, addition of chiral molecules in large enantiomeric excess that are, however, chiral only by virtue of isotope substitution causes a slight enantiomeric excess in the zinc alkoxide of the produced pyrimidyl alkanol. Asymmetric autocatalysis then leads to pyrimidyl alcohol with a large enantiomeric excess. The sense of enantiomeric excess of the product alcohol varies consistently with the sense of the excess enantiomer of the carbon isotopically chiral compound.