10. Addition Reactions

The following transformation is used as an early step in the synthesis of cilastatin, a drug used to counter antibiotic resistance. Identify a possible reagent for this step.

Predict the product of the following reactions.

(a)

Cyclopropanation using any of the reagents discussed here is stereospecific.

(b) Draw a reaction coordinate diagram for cyclopropanation.

In addition to radicals, anions, and cations, a fourth class of reactive intermediates is carbenes. A neutral species, the simplest carbene has a molecular formula of CH₂.

(h) Of the reactions studied here in Chapter 8, cyclopropanation is most similar to which?

To determine the stereochemistry of curacin A by synthesis, it would have been necessary to prepare all stereoisomers of the C₁₇―C₂₀ cyclopropane fragment. How would the reaction in Figure 16.30 be modified to produce the other stereoisomers shown here?

Nitrogen-containing heterocycles form particularly stable carbenes and are commonly used as ligands in organometallic chemistry. (a) Why is the carbene shown particularly stable? [It may be helpful to draw the molecular orbital picture.]

The reaction of an alkene with diazomethane forms a cyclopropane ring. Propose a mechanism for the reaction. (Hint: It is a concerted reaction.)

Show how you would accomplish each of the following synthetic conversions. 

a. trans-but-2-ene → trans-1,2-dimethylcyclopropane

Show how you would synthesize each compound using methylenecyclohexane as your starting material.

(g)

Propose mechanisms consistent with the following reactions.

(d)

When it is strongly heated, ethyl diazoacetate decomposes to give nitrogen gas and a carbene. Draw a Lewis structure of the carbene.

Show how you would accomplish each of the following synthetic conversions.

(c)

In addition to radicals, anions, and cations, a fourth class of reactive intermediates is carbenes. A neutral species, the simplest carbene has a molecular formula of CH₂.

(f) Cyclopropanation of (E)- and (Z)-3-methylhex-3-ene gives two different products. Rationalize this outcome.

Suggest a mechanism for the reaction shown in Figure 16.30 using IZnCH₂I as the cyclopropanating reagent.

Two chemists at Dupont found that ICH₂ZnI is better than diazomethane at converting a C=C bond to a cylcopropane ring. Propose a mechanism for the reaction, now known as the Simmons–Smith reaction in their honor.