Water influences the enantioselectivity in the proline or prolinamide-catalyzed aldol addition of acetone to isatins

The addition of small quantities of water to the proline or prolinamide-catalyzed aldol addition of acetone to isatin can result in increased enantioselectivity. DFT B3LYP calculations with a water molecule explicitly incorporated in the aldol transition states reproduce the observed enantioselectivity.

The addition of small quantities of water to the organo-catalyzed addition of acetone to isatin results in an increase in the ee of the reaction. DFT calculations with the inclusion of a water molecule in the aldol C-C TS reproduce the experimental ee.