[qw098]

Hey guys,

I had this question on my final (see below), and I was wondering if I got it correct! It seemed very basic, but I am unsure of the stereochemistry and of the alpha/beta nature of the ketone. The question was to show the major and minor products of the reaction.

On the 1-10 scale how right was I with 1 being dead wrong and 10 being 100% correct Thanks!

[Doc Oc]

Based on my personal experience with these types of compounds, I would say the ketone is actually the major product.  You need cerium or some other type of modifier to selectively reduce the ketone instead of the alkene.

But I don't know what answer your professor may have been looking for.

[fledarmus]

I agree with Doc Oc - without something like CeCl₃, I think this reaction gives mostly 1,4 addition of hydride across the enone, which then tautomerizes to the ketone on workup.

With a lanthanide, this is the Luche reduction giving the alcohol. I suspect that the hydride would attack from the less hindered face, giving the cis isomer as the major product.

[qw098]

Ahh ok cool! Yes, NaBH4 was used, and usually NaBH4 isn't such a strong reducing agent and would only be able to reduce till the ketone.

With a strong reducing agent like LiAlH4 my ketone would be totally reduced to the alcohol. Would the cis isomer predominate over the trans isomer?

[CaverKat]

Hydrides are pretty small nucleophiles.  Hydride attack of the carbonyl will occur from the axial face of the carbonyl.

1) 6 membered ring as a chair with methyl equatorial.
2) hydride attack of the carbonyl from the axial face.
3) get cis isomer (exclusively? i.e. kinetic? not sure)

That's for reduction of the ketone assuming there's no alpha-beta unsaturation....

[orgopete]

I hope this is an advanced organic class. Depending on what was expected, this gets complicated rather quickly. Borohydride reduction* of 2-cyclohexenone gives about a 50:50 mixture of cyclohexanol and cyclohexenol. Reduction of 2-methylcyclohexanone gives the trans alcohol as the major product. Stereochemistry of these reductions have been analyzed by many chemists and you may find an interesting review here. Since reduction of 2-methylcyclohexanone is a common lab experiment, you can find another analysis of it here.

Okay, let's add this all up. We don't have 2-cyclohexenone, but 6-methylcyclohex-2-enone. How will the methyl group affect conjugate addition? For 1,2-addition, we know the products of 2-methylcyclohexanone reduction gives mainly the trans alcohol, but now we have a neighboring double bond. How will that affect the reduction?

If this is an introductory class, the major may have been simply a 6-methylcyclohex-2-enol (as a mixture of isomers) and a minor of the 2-methylcyclohexanol (depending on the bias of the professor). If it were an advanced organic class, then I hope a similar or this exact example may have been discussed. As many of these questions ask, "What is the answer to a question in a class we didn't attend?"

*I don't have access to complete articles.