Hi:

Your question is a bit difficult to answer not knowing the organocatalyst you use, or a little more information on your substrate scope. However, the most common reasons for large %ee differences are the differences in the available conformers in the transition state. For example, the hydroxyl group may also coordinate to your reducing agent and force a single approach of the hydride to the ketone. I would suggest modeling your organocatalyst bound with your reducing agent (in whatever way is chemically plausible) and see which face of the different acetophenoes is accessible. This may be done very simply by using a model kit and much more complexly though TS calculations.

Good Luck!

As Cj mentioned, it is hard to say without more information. The answer may lie in the TS. May we know what is the catalyst you are using?

Hey Avtar, I asked about your organocatalyst just out of curiosity. You don't need to disclose it if you don't want.

Thanks

Nothing to add but the ketone plays a large role in how the catalyst directs the reducing agent as CJ suggests.

I think these results are not surprising. The substituent in 2-position is very close to the reaction center, and therefore may have influence on the transition state, which in turn is likely to have a big impact on the ee. This is especially true for a well-coordinating group like OH.

The same substituent in 4- or even 3-position might not have any effect on the ee.