24. Enolate Chemistry: Reactions at the Alpha-Carbon

Determine if the reaction is thermodynamically or kinetically controlled

The following are all substitution reactions, two of which we study in later chapters. With no knowledge of mechanism, what would you expect the ratio of products to be for each reaction, based on a random statistical distribution?

(a) Replacing a hydrogen (H) with deuterium (D):

A carboxylic acid is formed when an a-haloketone reacts with hydroxide ion. This reaction is called a Favorskii reaction. Propose a mechanism for the following Favorskii reaction. (Hint: In the first step, HO^- removes a proton from the a-carbon that is not bonded to Br; a three-membered ring is formed in the second step; and HO^- is a nucleophile in the third step.)

How could each of the following compounds be prepared from a ketone and an alkyl halide?

b.

How could each of the following compounds be prepared from a ketone and an alkyl halide?

a.

Show how the following ketones might be synthesized from the indicated acids, using any necessary reagents.

(b) methyl cyclohexyl ketone from cyclohexanecarboxylic acid

Predict the products of the following reactions.

(c)

Predict the major products of the following reactions.

How could each of the following compounds be prepared from cyclohexanone?

b.

How could each of the following compounds be prepared from cyclohexanone?

a.

Draw the products of the following reactions:

c. acetone + LDA/THF: (1) slow addition of ethyl acetate; (2) HCl

How could you prepare the following compound using a starting material that contains no more than three carbons?

Draw the products of the following reactions:

c.

Show how 4-methyl-3-hexanol can be synthesized from 3-pentanone.

Show how you would accomplish the following multistep conversions. You may use any additional reagents you need.

(a)