Chem 220 - Organic Chemistry

Problem Set 10

Chapters 11: The Chemistry of Ethers, Epoxides, Glycols and Sulfides

Due: November 28, 2011xxxxxxxxx


K. Barry Sharpless

Co-Nobelist 2001

Lecture: Video Text

Asymmetric Epoxidation and Dihydroxylation

 


 

Reading Assignment:

On the Epoxidation of Alkenes

Enrichment Assignment:

Diethyl ether (ether) may well be the first organic compound prepared that does not appear in Nature. For a chemical history of ether click here. A different Powerpoint version is here.
Theory of Etherification, A. W. Williamson, Quarterly J. Chem. Soc., 1852, 4, 106. [See page 106 in the .pdf file.]

"The following experiments were made with the view of obtaining new alcohols, by substituting carburetted hydrogen for hydrogen in a known alcohol. Iodide of potassium was readily formed on the application of a gentle heat, and the desired substitution was effected; but, contrary to expectation, the compound thus formed had none of the properties of an alcohol -- it was nothing else than common ether, C4H10O." On Etherification, A. W. Williamson, Quarterly J. Chem. Soc., 1852, 4, 229.


1. Each of the following reactions is missing a reactant, reagent and/or product. Provide the missing items along with an explanation.

2. A graduate student requires two related compounds:(±)- 2,2-dimethyl-3-isobutyloxirane (A) and (±)-2,5-dimethylhexan-2,3-diol (B). She has available to her isobutane as the only source of carbon. She decides to synthesize 2,5-dimethyl-2-hexene C, an alkene that can serve to provide both A and B.

a) Show her (your) synthesis of C.

b) Show how she can convert A into B and B into A.

3. Identify each of the structures below. Pay attention to stereochemistry. Pay attention to the equilibrium arrows in the equilibrium between A and I. Ignore any constitutional isomers that may arise.

4. Two oxidative pathways are shown below for the conversion of (E)-3-hexene 1 to propionaldehyde 4. The total electron change must be the same in both routes. Illustrate the electron change for each of the four steps.

5. Toprol (4; Lopressor; Metoprolol) is a β-blocker used for the treatment of hypertension. It is a racemic drug sold as its monosuccinate salt. A seasoned chemist wants to prepare Toprol as its (R)-enantiomer using the synthesis of the racemate. She follows the steps shown on the right.

a) Why is Toprol a racemate?

b) Draw a structure of the (±)-succinate salt.

c) What is the role of aq. NaOH? Check here.

d) What is the structure and CIP designation for 3?

e) What does the sequence of reactions and their chirality tell you about the mechanism of the double SN2 reaction sequence? e) Write mechanisms for the two reactions.

f) How can she prepare (S)-4 without resorting to the use of (R)-1?