Abstract
SEVERAL examples have been reported recently1 of antibody catalysis2of reactions that are strongly disfavoured because of the high free energy of the transition state. Here we show that catalytic antibodies can be used to promote a particularly useful kind of reaction from a synthetic point of view: one involving an intermediate that is highly unstable in water. We show that an antibody elicited against the quaternary ammonium ion 4a (Fig. 1) catalyses the protonation of the enol ether 1 to form, with complete enantio-selectivity, an oxocarbonium intermediate. This species is highly reactive in water, and would normally react with a water molecule to give the corresponding ketone 2. But the antibody provides a hydrophobic environment that allows the oxocarbonium ion instead to undergo an intramolecular reaction to form an enantiomerically pure ketal 3. This result shows that catalytic antibodies can exclude solvent molecules entirely from crucial steps on the reaction pathway.
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Shabat, D., Itzhaky, H., Reymond, JL. et al. Antibody catalysis of a reaction otherwise strongly disfavoured in water. Nature 374, 143–146 (1995). https://doi.org/10.1038/374143a0
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DOI: https://doi.org/10.1038/374143a0
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