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#1 2010-07-17 18:05:12

orgopete
Administrator

Mechanism of Corey-House condensation

www.chemicalforums.com wrote:

Mechanism of Corey-House reaction
Q: What's the role of a carbanion in the last step of Corey-House Synthesis?
Specifically:-

     R2CuLi + R'X   R-R'

And why does R' have to be primary?

I don't know the answer to this question either, but let me speculate somewhat.
*edit*
Lithium dialkylcuprate reacts with an alkyl halide (primary best; secondary and tertiary face elimination) in Et2O or THF. Primary dialkylcuprates work best; steric hindrance makes secondary and tertiary dialkylcuprates less reactive. The general halide reactivity pattern holds:  I > Br > Cl (with tosylate a better leaving group than any of the halogens).

You may also see the reaction suggested to be SN2-like. If it were an SN2-like reaction, then primary would be the best. I doubt this mechanism. I think it is more likely a direct attack on the halogen, hence iodide would be the most reactive. I think the electrons transfer to the copper for a net insertion reaction. If that were true, then because tertiary carbons donate electrons to the halogen, this would impede an addition to the halogen. The more negative the halogen is, the more resistant that halogen would be to accepting more electrons. A primary, without electron donating carbons, would be the easiest to add electrons from the copper to it.
***
Step two.
In my book, one of the things I did was to write mechanisms in a way that repeated electron movements of other reactions. That sometimes included writing a new mechanism for a reaction that was unknown or may have been written with another mechanism. Accordingly, I have included a copy of my discussion of a Gilman coupling with a vinyl bromide.

       http://www.curvedarrow.com/chem/ZZ43358AC7.jpg

Let's think about this reaction. In the first step (no mechanism) an electron rich copper (negative charge) is inserting into a C-Br bond. We might think that this insertion should be consistent with Grignard reactions and reactivity. That is, iodides might be more reactive than bromides, chloride or fluorides. Similarly, a vinyl bromide might be more reactive than an alkyl bromide as we may think of an sp2-carbon as more electron deficient (electron withdrawing) than an sp3-carbon. Accordingly, alkyl halides would further decrease in reactivity by addition of electron donating carbon atoms. Therefore, primary would be preferred.

While the insertion of an electron rich copper is suggested, it would be consistent with other reactions of Gilman or similar organocuprates. As you find in the reactions that follow, copper adds to enones and acyl chloride followed by similar bond forming reactions and loss of copper. You can see in the discussion above that I suggest a two electron process to parallel that of several other reactions.

In the discussion in the chemicalform link, someone suggested only primary halides due to steric hindrance. I do not believe that would be correct. If the mechanism is similar to Grignard formation, the mechanism of that reaction is not an SN2 substitution reaction and should not be guided by steric hindrance.

This example is excerpted from A Handbook of Organic Chemistry Mechanisms, available at http://www.curvedarrowpress.com/ or Amazon.com

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