25. Condensation Chemistry

Determine the product in the following conjugated addition reaction. 

Determine the product in the following conjugated addition reaction. 

Determine the product in the following conjugated addition reaction

(•••) FROM THE LITERATURE The following reaction was used in the synthesis of aculeatin A, a natural product that is active against KB cell lines. Although it only worked under acidic conditions, a mechanism can be drawn where the reaction might proceed under basic conditions. Suggest this mechanism (J. Org. Chem. 2014, 79, 1498–1504). [The most acidic proton is indicated . . . and number your carbons!]

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(•••) Lawsone, found in the extract of henna, reacts with amino acid residues to give the characteristic color associated with henna tattoos. Suggest a mechanism for the reaction shown.

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Predict the products of the following reactions.

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Show how an acetoacetic ester synthesis might be used to

form a δ-diketone such as heptane-2,6-dione.

Show reaction sequences (not detailed mechanisms) that explain these transformations:

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Show reaction sequences (not detailed mechanisms) that explain these transformations:

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Many of the condensations we have studied are reversible. The reverse reactions are often given the prefix retro-, the Latin word meaning “backward.” Propose mechanisms to account for the following reactions.

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Show how the following products might be synthesized from suitable Michael donors and acceptors.

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Show how the following products might be synthesized from suitable Michael donors and acceptors.

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Write equations showing the expected products of the following

enamine alkylation and acylation reactions. Then give

the final products expected after hydrolysis of the iminium salts.

(d) piperidine enamine of cyclopentanone + methyl vinyl ketone

Show how you would accomplish each conversion using an enamine synthesis with pyrrolidine as the secondary amine.

(a) cyclopentanone → 2-allylcyclopentanone

(b) pentan-3-one → 2-methyl-1-phenylpentan-3-one

(•••) FROM THE LITERATURE The following covalent inhibitor blocks function in a protease found in the porcine epidemic diarrhea virus by reacting with a cysteine amino acid residue (shown below) in the active site. Draw the expected complex that forms between the inhibitor and the enzyme active site (J. Med. Chem. 2017, 60, 3212–3216.) [Assume the presence of active site bases if you need them.]

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Show how the following products might be synthesized from suitable Michael donors and acceptors.

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In Solved Problem 22-9, the target molecule was synthesized using a Michael addition to form the bond that is β,γ to the upper carbonyl group. Another approach is to use a Michael addition to form the bond that is β,γ to the other (lower) carbonyl group. Show how you would accomplish this alternative synthesis.