19.3: Reactions of Enolates with Alkyl Halides

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Reactions of enolates with alkyl halides

Alkylation of enolates – can occur when an enolate reacts via an S_N2 mechanism with a low-lying \(σ^{*}\)_C-X, but it is very difficult to stop at monoalkylation.

Screen Shot 2023-01-04 at 10.35.38 AM.png

Other examples:

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Reactions involving chiral enolates give us an opportunity to create chirality since any transition state that forms is diastereomeric. Consider the following reaction:

Screen Shot 2023-01-04 at 10.36.01 AM.png

Let’s come back to this issue of double alkylation. Say we wanted to create the following complex ester by double alkylation of a simple ester. The problem is that a double alkylation product is formed.

Screen Shot 2023-01-04 at 10.36.13 AM.png

How do we avoid this? We perform a malonic ester synthesis:

Screen Shot 2023-01-04 at 10.36.22 AM.png

The malonic ester synthesis is a good way of making \(α\)-substituted esters and can be performed successively:

Screen Shot 2023-01-04 at 10.36.30 AM.png

What about using a similar strategy for making differentially substituted ketones? We can accomplish this by using the acetoacetic ester synthesis, the first step of which is a Claisen condensation.

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