13. Alcohols and Carbonyl Compounds

You might expect that aldehydes and ketones could undergo the addition/elimination mechanism. With strong nucleophiles, however, nucleophilic addition is the only outcome. Why?

Point out the flaws in the following incorrect Grignard syntheses.

(c)

(d)

A student added an equivalent of 3,4-epoxy-4-methylcyclohexanol to a solution of methylmagnesium bromide in diethyl ether, and then added dilute hydrochloric acid. He expected that the product would be 1,2-dimethyl-1,4-cyclohexanediol. He did not get any of the expected product. What product did he get?

Show how you would use Grignard syntheses to prepare the following alcohol from the indicated starting material and any other necessary reagents.

(a) octan-3-ol from hexanal, CH₃(CH₂)₄CHO

Which of the following is the correct final product when $\mathrm{PhMgBr}$ reacts with $\mathrm{acetone}$ followed by acidic workup in a Grignard reaction?

We discuss the reaction of Grignard reagents (organomagnesium compounds) to ketones in Chapter 17. Mechanistically, the reaction proceeds by the nucleophilic addition of a methyl carbanion to the electrophilic carbon of the carbonyl, breaking the C―Oπ bond, resulting in an alkoxide intermediate that is subsequently protonated to produce the 3° alcohol.

(b) Why, when the substrate is modified slightly, does the reaction result in an excess of one stereoisomer?

A student, when solving the following 'predict-the-product' question, made a common mistake by writing the answer shown here. Explain why this reaction would not work as written.

Draw the organic products you would expect to isolate from the following reactions (after hydrolysis).

(c)

(d)

Show two ways you could synthesize each of the following secondary alcohol by adding an appropriate Grignard reagent to an aldehyde.

(a)

In a Grignard reaction, what is the key bond that is formed during the reaction?

Show how you would add Grignard reagent to acid chloride or ester to synthesize the following alcohols.

a. Ph₃C–OH

Beginning with an amide, two different pathways produce the same compound. Predict the product of these two pathways.

List three different sets of reagents (each set consisting of a carbonyl compound and a Grignard reagent) that could be used to prepare each of the following tertiary alcohols:

b.