Enolates in Organic Synthesis – a Comprehensive Practice Problem

This is a comprehensive practice problem on the alpha carbon/enolate chemistry. The topics covered range from the simple halogenation reactions of enols to multistep synthetic transformations.

To correctly answer these questions, you need to review the main principles of enolate chemistry – direct enolate alkylation, aldol condensation, crossed aldol condensation, alkylation using acetoacetic ester synthesis, malonic ester synthesis, the Stork enamine synthesis, Claisen condensation, Michael addition, and Robinson annulation.

Check the links below if you are looking for practice problems on specific topics in alpha carbon chemistry:

 

 

Practice

1.

Propose an efficient strategy to achieve each of the following synthetic transformations and show the structure of all the key intermediates.

 

a)
Answer

The starting material is a cyclic acetal which serves as protecting groups for aldehydes and ketones. Therefore, it needs to be removed first before the alkylation of the alpha carbon can occur. Notice that the alkylation occurs at the less substituted carbon since LDA is used as a strong, sterically hindered base which favors the kinetic product in direct alkylation of enolates.

b)
Answer

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c)
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d)
Answer

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e)
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f)
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g)
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h)
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i)
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j)
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k)
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l)
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m)
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n)
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o)
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p)
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q)
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r)
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s)
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t)
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u)
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v)
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w)
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x)
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y)
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z)
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