Spring 2008

Workshop #1

Part 1:

Consider the reaction of the epoxide shown below under either acidic or basic conditions to yield a ring-opened product. Proceed by answering the following directed questions in order. Notice that the starting epoxide is the same, but the regiochemistry of reaction changes for basic versus acidic conditions.
First consider BASIC reaction conditions.

·  Which reactive species is present in an methanolic solution of base?

·  What is the charge on the reactive species? Characterize the reactive species as a Lewis acid or Lewis base (remember that Lewis acid is the same as electrophile and Lewis base is the same as nucleophile).

·  Does more than one electrophilic site exist in the epoxide?

·  Given the reactive species that you identified above, where will it attack the epoxide (oxirane)? Will your nucleophile attack one position preferentially? Which one and why?

·  With the help of the curved arrows, show the movement of electrons that corresponds to the reaction between the epoxide molecule and your reactive species.

·  Draw the structure of the product formed by this mechanism.

·  Is this intermediate (product) cyclic or acyclic?

·  What will the charge be on this intermediate? Is it a Lewis acid or Lewis base?

·  What's the role of the sodium cation at this point in the mechanism?

·  Realizing that this is a base-catalyzed reaction, we have to (at the end of the day) end up with a NEUTRAL organic molecule and regenerate the methoxide (base) catalyst. Show with the help of curved arrows how the final product is formed from your intermediate.

·  Does the reaction follow an SN1-type pathway or SN2-type pathway?

Now consider ACIDIC conditions:

·  Which reactive species is present in an aqueous solution of acid?

·  What is the charge on the reactive species? Characterize the reactive species as a Lewis acid or Lewis base (remember that Lewis acid is the same as electrophile and Lewis base is the same as nucleophile).

·  Given the nature of our catalyst and the electronic characteristics of the epoxide, what do you think will happen? Where will it interact with the epoxide (oxirane)?

·  With the help of the curved arrows, show the movement of electrons that corresponds to the reaction between the epoxide molecule and your reactive species.

·  Draw the structure of the intermediate formed by this mechanism.

·  Is this intermediate (product) cyclic or acyclic? Charged or uncharged?

·  Show with the help of curved arrows how the intermediate species #1 can alter itself to disperse charge.

·  At this point, identify the major Lewis acid and Lewis base present in the reaction and use them to complete the mechanism being sure to regenerate your catalyst.

·  Does the overall reaction follow an SN1-type pathway or SN2-type pathway?

Part 2:

Complete the following series of functional group interconversions using your Jones text as a guide -- do not work the mechanism at this point. Assume that conditions lead primarily to SUBSTITUTION (ignore any competing elimination reactions).


·  Verify that each of your structures is correct by working through the mechanism for each step (except C to D). Each workshop student should select a step, derive the mechanism, and then present to the group on the blackboard. Were any structures wrong? Why?

·  For which reaction in the sequence would a competing elimination pathway be most significant? Explain. (HINT: look at the reagents and reaction conditions in consultation with SAM page 9)

·  What’s the purpose of the conversion of C to D?

Part 3:

1.  3-Bromo-3-methyl-1-butene forms two substitution products when it is added to a solution of sodium acetate in acetic acid.

(a)  Give the structures for the two expected regioisomeric substitution products.

(b)  Under kinetically controlled reaction conditions which of the two products is the major product? Explain.

(c)  Under thermodynamically controlled reaction conditions which of the two products is the major product? Explain.

2. 
Propose a mechanism for the following reaction.


3. When the following stereoisomer of 2-chloro-1,3-dimethylcyclohexane reacts with sodium methoxide in methanol, only one product is observed. However, when the reaction conditions are changed so that the reaction is conducted in pure methanol, eight products are observed. Identify the various products that form under the two different reaction conditions and provide mechanisms that account for their formation.