[RaZ]

Hi, quick question hopefully.  How exactly does a metal on an enolate help the stereoregulation in an aldol reaction such as this:  http://upload.wikimedia.org/wikipedia/commons/d/d7/Metalion.gif

Basically I'm wondering why you would need a metal ion even if you're using an enolate with a chiral auxillary such as this: http://upload.wikimedia.org/wikipedia/commons/c/ca/Evansaldol5.gif (the boron being the metal there).  How does the metal help in stereoselectivity here even though you have the chiral auxilaries next to the imide directing the reaction?

Thanks.

BTW: you can read about Evans' oxazolidinone chemistry here: http://en.wikipedia.org/wiki/Aldol_reaction#Evans.27_oxazolidinone_chemistry

[movies]

You have to have a metal in order to make the enolate.  The keto/enol equilibrium isn't enough.

Think about the point where you make the carbon-carbon bond (and thus the two new stereocenters.  How is the metal involved at that point?

[RaZ]

Well I understand that the metal may have directing effects on how the aldehyde will approach the enolate.  But my main question I guess is why do you require a metal (other than to make the enolate) when doing aldol with oxazolidinone as in this: http://en.wikipedia.org/wiki/Aldol_reaction#Evans.27_oxazolidinone_chemistry 

What steric effects does the metal have when you have a chiral auxiliary on the enolate?  or does the metal also have something to do with the product formed?

[RaZ]

oh and here's the mechanism for that aldol reaction....

[movies]

There is some information you need that apparently isn't included on the page you linked to.  I'll try to explain.

Every aldol reaction has two possible mechanisms: a closed transition state (Zimmerman-Traxler type, described at length on the page) and an open transition state (not discussed on the page).  The open transition state differs because it has separate Lewis acids coordinated to the enolate and the aldehyde.  The way these transtion states are usually shown is through Newman projections:

There are four because you have two faces of the enolate and two faces of the aldehyde which you could potentially attack (there are 4 more for the E enolate isomers, I arbitrarily chose to draw Z).  From those four TS, you get two sets of diastereomers.  You can rationalize which TS is best by steric arguments.  Note that the preferred product from an open TS is not always the same as the preferred product of a closed TS.

Selecting the right metal is obviously critical in determining whether or not the aldol prefers and open or closed TS.  For an open TS, you want Lewis acids that can only coordinate one thing at a time.  The best example of open TS aldol chemistry is the Mukaiyama aldol, where your enol equivalent is a silyl enol ether, and therefore can't coordinate to another Lewis acid.

The choice of metal is important to reactions that you want to go through a closed TS because you need to suppress the open TS pathway.  Boron happens to be very good at this.  The sterics of the metal itself aren't important, but the ligands hanging off of the metal are.  In the Evans aldol, the butyl groups on B provide important steric interactions in the closed TS that eliminate some of the possible TS, and the size of the Lewis acid may also disfavor open TS, but I'm not sure about that.

Does this answer your question?  There are a lot of subtleties to aldol chemistry, but they have been studied a lot, so there are good explanations for most of them.

[RaZ]

Hey, thanks a lot...I knew about the Zimmerman-Traxler type aldol reactions but never the 'open transition state' reactions...this definitely helps.  Thanks again.

[RaZ]

Quick question; so in the case of lithium which isn't able to coordinate two things at once, it will go through an open transition state right?

[movies]

Lithium can (and does) coordinate more than one thing.  The only LAs that can really only coordinate one thing are the ones that become coordinatively saturated after binding one other site.  A good example is BF₃.