Presidential Young Investigator/Development of Chiral, Self-Replicating Molecules

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Self-reproduction is a central feature of living systems but is almost unprecedented in simple chemical systems. A promising system to be studied to initiate the development of such capacity in a chemical system is the reaction of an achiral alpha-heteroaldehyde with a dialkylzinc reagent. Dialkylzinc addition to aldehydes is normally a very slow reaction but can be catalyzed by the zinc alkoxides produced in the reaction and thus these systems show autocatalytic behavior. Recent studies showed that the ethylzinc salt of (R)-1-phenylpropanol (70%ee) catalyzes the addition of diethylzinc to benzaldehyde, producing (R)-1-phenylpropanol (17%ee). In this system the chiral catalyst generates its own enantiomer from achiral starting materials as it must to reproduce itself, but the reaction's low enantioselectivity leads to mainly a racemic mixture; much better enantioselective catalysts have been developed for the addition of diethylzinc to benzaldehyde. They all incorporate a second coordination site in the alkoxide, usually a nitrogen. The goal of this work is to design a system where an achiral aldehyde substrate leads to a chiral alkoxide which is an efficient, enantioselective catalyst for its own formation. One of the most remarkable features of the aminoalcohol catalyst systems is that they show a positive nonlinear effect. The monomeric alkoxides are the active catalysts, but they will dimerize in solution to give inactive dimers. The racemic dimer which is the most stable, is in effect removed from the catalytic system, thus increasing the enantioselectivity. Monomeric and dimeric structures of the catalysts will be designed and modeled to produce a positive nonlinear effect by this mechanism. A successful reaction system will produce a chiral alkoxide with increasing enantiomeric excess as the reaction proceeds. Dr. Scott Rychnovsky is being given the Presidential Young Investigator Award from the Synthetic Organic Chemistry Program to support his research to develop chiral, self-replicating molecules. This work has the potential to revolutionize how the complex chiral molecules will be synthesized in the future and completely change the nature of the strategic plans that are developed by the chemist in attacking new structures.