Carbon Isotope Chirality Triggers Asymmetric Reaction

Enantiomeric molecules that are chiral only because of substituents that have different carbon isotopes can generate chirality in asymmetric autocatalysis—a reaction in which a chiral product does double duty as a chiral catalyst for its own production (Science, DOI: 10.1126/science.1170322). Although there are examples of enantioselective reactions and kinetic resolutions of two enantiomers induced by hydrogen isotopes, this is the first example in which enantioenrichment has been achieved solely on the basis of carbon isotopes. The finding, from Kenso Soai and coworkers of Tokyo University of Science, could provide a clue to determining why there is a natural abundance of one enantiomer in certain natural chiral molecules, such as amino acids. Because ¹³C and ¹²C are so similar, it's difficult to chemically discern molecules that are chiral solely because of their isotopic substitution. Soai's group managed the trick via the asymmetric autocatalytic reaction between pyrimidine-5-carbaldehyde and diisopropylzinc to form a pyrimidyl alcohol. They found that adding a zinc alkoxide made from an isotopically substituted chiral alcohol, such as dimethylphenyl methanol, would lead to a slight enantiomeric excess of pyrimidyl alkanol product. The enantiomeric excess of the resulting pyrimidyl alcohol then becomes amplified, thanks to asymmetric autocatalysis.