carbonyl alpha substitution

MS 935 - Enols and Enolates Submitted by Matt on August 7, 2011.

Textbook and Chapter: Carey and Giuliano 8th Ed. (2010), Chapter 20

Keyword: carbonyl alpha substitution

Description: Goes over how to form enols/enolates under acidic and basic conditions, and how enols/enolates react.

Total Problems: 6

Problem # 750

Let's work through a Robinson annulation.

Work backwords to determine the starting materials needed to produce each intermediate below, then show a mechanism for the overall reaction.

Problem # 749

Show how to prepare each compound below from propanal. I've marked the "cuts" for you.

Problem # 748

Alpha bromination is usually carried out under acidic conditions via the enol intermediate. 

Alpha bromination is uncontrollable under basic conditions, which goes through the enolate intermediate. Let's explore why.



a) Rank each carbonyl below in order of decreasing alpha-proton acidity (1= most acidic). Explain.

b) based on a), why does the reaction below lead to polyhalogenation?

Problem # 747

Show a combination of enolate (nucleophile) and electrophile that can produce each compound below.

Remember that all enolates come from carbonyls.

Problem # 746

Show what combination of aldehyde, ketone, and/or ester can prepare each compound below. Every compound is a Claisen or aldol product.

Problem # 743

Enolates are nucleophiles and react with a variety of electrophiles.

Carbonyls are electrophiles. But aldehydes/ketones and  esters/acid chlorides often form different products.


Use curved arrows to draw a mechanism for each reaction below. How do the two products differ?

Problem # 742

Enamines are similar to enols and enolates in that they also undergo alpha substitution reactions.

The process of performing a carbonyl alpha substitution reaction via an enamine intermediate is called the Stork enamine synthesis. Let's work through this reaction.


Draw in the structures for the enamine and show it attacking the alkyl halide to form the  "3º imine." Also draw the structure of the final and carbonyl product.


Problem # 741

Like enolates (Q740), enols can also act as nucleophiles and make new bonds at the alpha position.

Let's go through the mechanism for how this happens, using alpha bromination as our example.

In the reaction below, the carbonyl form is in equilibrium with its enol form (Q738), which can then attack molecular bromine.


Complete the structure of the protonated carbonyl, and show the curved arrows that transform it into the final carbonyl product.

Problem # 740

Enolates are formed from carbonyls by adding a strong base, such as lithium diisopropyl amide (LDA), to deprotonate the alpha position. The enolate can then act as a nucleophile and attack an electrophile (such as an alkyl halide), to form a new bond at the alpha position. This is called a carbonyl alpha substitution reaction.


Let's go through the mechanism of how enolates are formed and how they react with electrophiles.

Draw in the curved arrows to show the formation of the enolate (middle compound), and draw the structure of the carbonyl product (right compound)