13. Alcohols and Carbonyl Compounds

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

Point out the flaws in the following incorrect Grignard syntheses.

(b)

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.

(a) Propose a mechanism to show how the reaction of ethyl formate with an excess of allylmagnesium bromide gives, after protonation, hepta-1,6-dien-4-ol.

Show how to make these deuterium-labeled compounds, using CD₃MgBr and D₂O as your sources of deuterium, and any non-deuterated starting materials you wish.

d. Ph(CD₃)₂COD

Show how to make these deuterium-labeled compounds, using CD₃MgBr and D₂O as your sources of deuterium, and any non-deuterated starting materials you wish.

b. CH₃C(OH)(CD₃)₂