Chiral Catalysts in Reactor

Sorry if this is a double post- I did a quick search but didn't see anything relevant to my question.

 

I'm trying to use reactor for a reaction where the stereochemistry of the product is based on the chirality of the catalyst going in. In the case I am working with, the product class has three chiral centers (W/W/H or H/H/W) depending on if the catalyst used is R or S.

 

Is there an easy way to define the stereochemistry of the product as a function of the chirality of a reactant which is not represented in the product? If not, it's a small enough enumeration that we can just draw out the products by hand. Thanks in advance..

 

-Jim

Thank you for this interesting question. I think, that I cannot answer this question without seeing the reaction schem and some examples with expected result. Do you have some images to share? So,  I am not sure how relevant is this idea, but  one approach might be to perform the reaction in two steps. First generate the specific transition states that include catalyst in the product. Then in the second step you can use the transition states as reactants and remove the catalyst resulting stereospecific products.

In the future we plan to support multistep reaction schemes will be supported in the future (do not ask when ;) ), so you will be able to refer to the transition state or intermedier in a single scheme even from the reaction rules.
We plan to support (s) and (r) stereochemistry (pseudo-asymmetric atoms) in the future as well.

 

Sure- see attached. It's a work in progress (obviously!)

The third reactant is what dictates the stereochemistry of the product.

 

 

Reactant R (hashed bond) --> 11/1 hashed, 13/3 hashed, 8/2 wedge

Reactant S (wedge bond) --> 11/1 wedge, 13/3 wedge, 8/2 hashed

 

By no means is this an easy one! Thanks for your help.

Jim

Thank you, for the example! Can you imagine generating a non-stereo output that you can convert to the expected stereo with reactor or standardizer in a second step?

We use Reactor as a tool for actual library enumeration as opposed to a virtual sample browser, so I'm not sure we could. The array we are working with incorporates both catalysts in the same library, and we'd need to track which is which. Just for the record, how would you recommend working this in two steps?

 

The enumeration is slated for less than 50 compounds for the time being- it may be easier on our end to draw them by hand (though I'm not one to give up quickly on a problem like this).

 

Thanks- rest assured that I'll keep on this, even if we don't need the solution right away!

-Jim

The best if you do it manually now. Without pseudo-asymmetry we can just think in some workarounds. You can for example generate non-stereo products, then enumerate all stereoisomers of the products with the help of the stereoisomer plugin and then select the feasible ones by a query containing the scaffold with the desired stereo configuration. It is not an elegant approach, but it can save time if you have a much larger library.

Ah yes- I see what you mean now.

We're fine with the workaround for the time being. Thanks for your help!

-Jim

Thank you, Jim, for highlighting this interesting stereochemistry issue.