13. Alcohols and Carbonyl Compounds

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

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

In a Grignard reaction, which key feature is formed as a result of the reaction between a Grignard reagent and a carbonyl compound?

The Grignard reaction is based on the chemistry of what type of species?

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.

(a) Why does this reaction produce a racemic mixture of 3° alcohols?

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?

In Chapters 8 and 17 we learn two reactions for the synthesis of the alcohol shown. (a) Show a mechanism for each of the reactions. (b) If you were designing a synthetic route, which would be considered more sustainable? Consider all factors. [Assume the starting organic molecules are equally green.]

Starting from bromobenzene and any other reagents and solvents you need, show how you would synthesize the following compounds. Any of these products may be used as starting materials in subsequent parts of this problem.

b. 1-phenylpropene

Which of the following compounds are suitable solvents for Grignard reactions?

(a) n-hexane

(b) CH₃–O–CH₃

(c) CHCl₃

(d) cyclohexane

(e) benzene

(f) CH₃OCH₂CH₂OCH₃

(g)

(h)

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

(c)

(d)

A formate ester, such as ethyl formate, reacts with an excess of a Grignard reagent to give (after protonation) secondary alcohols with two identical alkyl groups.

(b) Show how you would use reactions of Grignard reagents with ethyl formate to synthesize the following secondary alcohols.

(i) pentan-3-ol

(ii) diphenylmethanol

(iii) trans,trans-nona-2,7-dien-5-ol

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

Often, compounds can be synthesized by more than one method. Show how this 3° alcohol can be made from the following:

(a) two different ketones