Organic Chemistry CHM 252 and CHM 254L

CHM 252 Organic Chemistry II
Spring 2001
Workshop #11

1.  A good example of a classic aldol reaction involves 2-butanone and acetone.  However, notice that there are MULTIPLE acidic protons in each of these starting materials (a to the carbonyl).   Consequently, we can envision that there are a variety of combinations of enolate (nucleophile) and electrophilic carbonyls that could lead to a whole mess of products.   It is your job in this problem to identify each of the possible nucleophile (enolate) and electrophile combinations and the product structures that their interactions generate by competing the table below (be careful of E vs. Z stereochemistry for any alkene containing products).

2.  Show the complete mechanism of reaction for any ONE of the products generated in question #1.

3.  The Claisen-Schmidt modification of the aldol reaction is an example of a crossed-aldol reaction that allows the organic chemist to selectively create a single aldol product.  What is the Claisen-Schmidt modification?   Suggest a pair of compounds that will yield a SINGLE aldol product.

4.  One very powerful way to create carbocyclic systems is to employ aldol chemistry in an intramolecular fashion.  The classic example is the Robinson annulation reaction of which an example is shown below.  Work through the mechanism of the reaction to show how the cyclized product arises from the starting material.

5.  Can you suggest one other cyclized product that could potentially form (side-product)?

6.  The starting material in question #4 was generated using the Michael reaction (enolate attack on an a,b-unsaturated carbonyl system) as shown below.  Show the mechanism for the conversion of the starting materials into the designated product.

(a) Do you think the enolate is generated at position #1 or position #2?   Explain.
(b) Why do you think that the enolate (once generated) will attack at position #3 rather than at the carbonyl carbon? Explain.
(c) Do you think that CH₃MgBr (as a nucleophile) will more likely attack at position #3 or the carbonyl carbon?  Explain. 

NOTE: your answers here depend upon identifying whether your attacking nucleophile is soft (weak base) or hard (strong base).

7.  Complete the sequence of reactions shown below.  HINT: step #1 involves an intramolecular Claisen condensation and step #2 involves some acetoacetic acid chemistry followed by NAcS.

8.  Which proton will be removed by NaOEt in step #2 of the reaction in question #7?  Why?

Timm A. Knoerzer
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Naz Chem. Dept.
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Last Updated Wednesday, April 18, 2001 11:41:32 AM