A specific example of how chirality influences pKa in asymmetric catalysis is found in the Sharpless epoxidation reaction, where chiral catalysts selectively modify the pKa of certain protons in allylic alcohols. In this reaction, a chiral catalyst (usually a titanium complex with a chiral tartrate) coordinates with the allylic alcohol, creating an asymmetric environment that stabilizes the deprotonation of the alcohol selectively on one face of the molecule.
This selective coordination lowers the effective pKa of the hydroxyl group on one face, favoring deprotonation and subsequent epoxidation on that side. This interaction doesn’t change the intrinsic pKa of the functional group but effectively biases the reaction pathway, creating a distinct difference in reactivity between the two enantiotopic faces of the molecule due to the chiral catalyst.
This example demonstrates how asymmetric catalysts can influence acid-base behavior, even if the pKa change is not intrinsic but rather a function of the catalyst-substrate complex. Such chiral modifications of pKa values are particularly valuable in stereoselective synthesis, where controlling reactivity at specific sites can be crucial for achieving high enantioselectivity.