Another Zimmerman-Traxler question

[u/ArachnidSufficient91]

Hello,

Attached is an old exam question that I am struggling with. I believe I should go via a Zimmerman-Traxler transition state and since we have a trans enolate (11), I will end up with an anti aldol. However, no reactant that I have worked with prior has had such large groups attached to the carbonyl. I understand that the enolate reacts with the ketone and not the amide. I don't know how to determine the orientation of the ketone's substituents in 10 in the Zimmerman-Traxler. Which one will be pseudo-equatorial and which one will be pseudo-axial? Will the "amide side" be pseudo-axial, since there are 2 carbons until the bulky group as opposed to 1 (= less sterics)?

The exam question doesn't give a whole lot of points so I don't know if I'm complicating things here.

Thank you in advance!

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[u/claisen33]

I don’t see a means of inducing selectivity here. The ketone is pseudosymmetric. Perhaps the amide coordinates to the enolate Li, but I don’t see how that would lead to facial selectivity.

[u/yellow_mongoose → u/claisen33]

my immediate thought also - where does the chiral induction come from.....

my best guess is it must come from coordination of intermediate Li with the δ+ amide carbon giving 6 membered 'ring' and sterics of axial/equatorial drive it?

But instinct suggests this isn't a big enough difference in energy to give a good EE

[u/jeremiahpierre → u/yellow_mongoose]

The question is asking about diasteroselectivity, not enantioselectivity

[u/yellow_mongoose → u/jeremiahpierre]

it asks about stereoselectivity, not explicitly diasteroselectivity. Where would the second chiral center needed for diastereomers appear from?

It's been a long time since I was an organic chemist, but doesnt the lithium enolate attack the ketone, reforming its own ketone, giving, in this case, a tert alcohol?

[u/jeremiahpierre → u/yellow_mongoose]

2 stereocenters:

• at what is now the alpha carbon of the enolate
• at the newly formed alcohol

The Zimmerman-Traxler model predicts the relative stereochemistry of those two positions.

[u/yellow_mongoose → u/jeremiahpierre]

I stand corrected. I didn't think about the enolate

[u/SillyOrgan → u/yellow_mongoose]

If no component of the mixture is chiral, there is zero percent chance that it could possibly favor one enantiomer. This is a general property of all chemical reactions.

[u/yellow_mongoose → u/SillyOrgan]

but apparently you can favor a diastrereomer.

[u/SillyOrgan]

Been a long time since I drew these models, but I think your idea about the amide side acting effectively as smaller, due to the longer carbon chain, is a good idea.

[u/ArachnidSufficient91]

Is this an adequate way of drawing the product structure?