Carbonyl Condensation Reactions

Question: Draw the aldol product formed from each compound.

Question: Which carbonyl compounds do not undergo an aldol reaction when treated with OH^- in H₂O ?

Question: What unsaturated carbonyl compound is formed by dehydration of each β-hydroxy carbonyl compound?

Question: Acid-catalyzed dehydration of β-hydroxy carbonyl compounds occurs by the mechanism discussed in Section 9.8. With this in mind, draw a stepwise mechanism for the following reaction.

Question: What aldehyde or ketone is needed to prepare each compound by an aldol reaction?

Question: 2-Pentylcinnamaldehyde, commonly called flosal, is a perfume ingredient with a jasmine-like odor. Flosal is an $\mathit{\alpha }\mathbf{,}\mathit{\beta }$ -unsaturated aldehyde made by a crossed aldol reaction between benzaldehyde $\left(C_6{H}_{5}CHO\right)$ and heptanal $\left(C{H}_{3}C{H}_{2}C{H}_{2}C{H}_{2}C{H}_{2}C{H}_{2}CHO\right)$, followed by dehydration. Draw a stepwise mechanism for the following reaction that prepares flosal.

Question: Draw the products formed in each crossed aldol reaction.

a.

b.

Question: Draw the products formed in the crossed aldol reaction of phenylacetaldehyde $\left(C_6{H}_{5}C{H}_{2}CHO\right)$ with each compound: (a) $\mathit{C}{\mathit{H}}_{\mathbf{2}}{\left(COOEt\right)}_{\mathbf{2}}$ ; (b) $\mathit{C}{\mathit{H}}_{\mathbf{2}}{\left(COC{H}_3\right)}_{\mathbf{2}}$ ; (c) $\mathit{C}{\mathit{H}}_{\mathbf{3}}\mathit{C}\mathit{O}\mathit{C}{\mathit{H}}_{\mathbf{2}}\mathit{C}\mathit{N}$.

Question: What aldol product is formed when two molecules of butanal react together in the presence of base? What reagents are needed to convert this product to each of the following compounds?

Question: What carbonyl starting materials are needed to prepare each compound using a directed aldol reaction?

Question: Zingerone, a spicy-sweet component of cooked ginger, can be converted to its protected TBDMS ether A, as we learned in Chapter 20. How can A be converted to gingerol, a compound present in fresh ginger, using a directed aldol reaction as a key step?

Question: A key step in the synthesis of donepezil (trade name Aricept) is a directed aldol reaction that forms $\mathit{\alpha }\mathbf{,}\mathit{\beta }$-unsaturated carbonyl compound X. What carbonyl starting materials are needed to prepare X using a directed aldol reaction? What reagents are needed to convert X to donepezil?

Question: Draw a stepwise mechanism for the conversion of heptane-2,6-dione to 3-methylcyclohex-2-enone with NaOEt, EtOH.

Question: What cyclic product is formed when each 1,5-dicarbonyl compound is treated with aqueous  $\mathit{O}\mathit{H}$?

Question: Following the two-step reaction sequence depicted in Figure 24.5, write out the steps needed to convert A to B.

Question: What β-keto ester is formed when each ester is used in a Claisen reaction?

Question: What crossed Claisen product is formed from each pair of compounds?

a.

b.

Question: Avobenzone is a conjugated compound that absorbs ultraviolet light with wavelengths in the 320–400 nm region, so it is a common ingredient in commercial sunscreens. Write out two different crossed Claisen reactions that form avobenzone.

Question: Draw the products of each reaction.

Question: Two steps in a synthesis of the analgesic ibuprofen, the chapter-opening molecule, include a carbonyl condensation reaction, followed by an alkylation reaction. Identify intermediates A and B in the synthesis of ibuprofen.

Question: What two β-keto esters are formed in the Dieckmann reaction of the following diester?

Question: Which of the following compounds can serve as Michael acceptors?

Question: What product is formed when each pair of compounds is treated with NaOEt in ethanol?

Question: What starting materials are needed to prepare each compound by the Michael reaction?

Question: Draw the products when each pair of compounds is treated with $\mathit{C}{\mathit{H}}_{\mathbf{3}}\mathit{C}{\mathit{H}}_{\mathbf{2}}{\mathit{O}}^{\mathbf{-}}\mathbf{,}\mathbf{ }\mathit{C}{\mathit{H}}_{\mathbf{3}}\mathit{C}{\mathit{H}}_{\mathbf{2}}\mathit{O}\mathit{H}$  in a Robinson annulation reaction.

Question: Which of the following bicyclic ring systems can be prepared by an intermolecular Robinson annulation?

Question: What starting materials are needed to synthesize each compound by a Robinson annulation?

Question: Draw the aldol product formed from each pair of starting materials using $\mathit{O}\mathit{H}\mathbf{,}\mathbf{ }{\mathit{H}}_{\mathbf{2}}\mathit{O}$.

Question: What steps are needed to convert A to B?

Question: Draw the product formed from an aldol reaction with the given starting material(s) using $\mathit{O}\mathit{H}\mathbf{,}\mathbf{ }{\mathit{H}}_{\mathbf{2}}\mathit{O}$ .

Question: Draw the product formed in each directed aldol reaction.

Question: Draw the product formed when each dicarbonyl compound undergoes an intramolecular aldol reaction followed by dehydration.

Question: What starting materials are needed to synthesize each compound using an aldol or similar reaction?

Question: What product is formed when a solution of A and B is treated with mild base? This reaction is the first step in the synthesis of rosuvastatin (sold as a calcium salt under the trade name Crestor), a drug used to treat patients with high cholesterol.

Question: What dicarbonyl compound is needed to prepare each compound by an intramolecular aldol reaction?

Question: Identify the structures of C and D in the following reaction sequence.

Question: Explain why ketone K undergoes aldol reactions but ketone J does not.

Question: Draw the Claisen product formed from each ester.

Question: Draw the product formed from a Claisen reaction with the given starting materials using –OEt, EtOH.

Question: What starting materials are needed to synthesize each compound by a crossed Claisen reaction?

Question: Even though B contains three ester groups, a single Dieckmann product results when B is treated with $\mathit{N}\mathit{a}\mathit{O}\mathit{C}{\mathit{H}}_{\mathbf{3}}$ in $\mathit{C}{\mathit{H}}_{\mathbf{3}}\mathit{O}\mathit{H}$, followed by ${\mathit{H}}_{\mathbf{3}}{\mathit{O}}^{\mathbf{+}}$. Draw the structure and explain why it is the only product formed.

Question: Draw the product formed from a Michael reaction with the given starting materials using $\mathit{O}\mathit{E}\mathit{t}\mathbf{,}\mathbf{ }\mathit{E}\mathit{t}\mathit{O}\mathit{H}$ .

Question: What starting materials are needed to prepare each compound using a Michael reaction?

1. Question: β -Vetivone is isolated from vetiver, a perennial grass that yields a variety of compounds usedin traditional eastern medicine, pest control, and fragrance. In one synthesis, ketone A is converted to β-vetivone by a two-step process: Michael reaction, followed by intramolecular 00a00000ldol reaction.000 (a) What Michael acceptor is needed for the conjugate addition? (See Problem23.61 for another method to form the bicyclic ring system of β-vetivone.) (b) Draw a stepwise mechanism for the aldol reaction, which forms the six-membered ring.

Question: Draw the product of each Robinson annulation from the given starting materials using $\mathit{O}\mathit{H}$ in ${\mathit{H}}_{\mathbf{2}}\mathit{O}$ solution.

Question: What starting materials are needed to synthesize each compound using a Robinson annulation?

Question: Draw the organic products formed in each reaction.

Question: Fill in the lettered reagents needed for each reaction.

Question: What product (including stereochemistry) is formed in each of the following intramolecular reactions?

Question: Identify compounds A and B, two synthetic intermediates in the 1979 synthesis of the plant growth hormone gibberellic acid by Corey and Smith. Gibberellic acid induces cell division and elongation, thus making plants tall and leaves large.