8.7 Aldol Reactions

8.7 Aldol Reactions

• In this chapter, we've learned how to make enolates, and we've used them to attack various electrophiles.
• We will look at what happens when an enolate attacks a ketone or aldehyde.

• Suppose we use hydroxide as a base and start with a simple ketone.

• The enolate can attack the electrophile if we do this.
• The equilibrium will replenish the supply.

• It turns out that there is more than one person present.
• There is a lot of ketone present and the enolate is in equilibrium with it.
• When ketones are attacked, we devoted an entire chapter to the reactions that take place.

• An alkoxide intermediate is formed when the enolate attacks the ketone.
• Our golden rule is to try and re-form the carbonyl group, but not expel H- or C-.
• We can't leave groups that can be expelled.
• There is only one way to remove the charge.

• This is the beginning of the reaction.

• Whenever an enolate attacks a carbonyl group, the structure of the enolate will always be the same.
• The carbonyl group of the ketone is being attacked by the alpha carbon of the enolate.
• The OH group will always be in the alpha position.

• The reaction doesn't stop at the b-hydroxy ketone.

• The product has a double bond with the carbonyl group.
• Between the a and b positions is where the double bond is located.

• We can control how far the reaction goes in the laboratory.
• Carefully controlling the conditions of the reaction.

• You should know the proper terminology.
• A small molecule is liberated in a condensation reaction.
• The small molecule can be either N or CO.

• We can't call it a condensation reaction if a water molecule is not lost in the process.
• We call it an aldol addition.

• The mechanism of aldol condensation is easy to understand.
• It can be difficult to see what reagents to use in a synthesis.

• Two alpha protons and an oxygen atom are being removed from one ketone.
• The curved arrows and intermediates are shown in a mechanism.
• This way of thinking about the reaction might be useful when proposing a new drug.

• We will get practice with the mechanism to get the answer.
• We need to make sure that we can use our simple method for drawing the expected product.

• It's an efficient way to draw the product.

• If there is a condensation, draw the a,b-unsaturated ketone that is produced.

• One molecule of ketone was deprotonated to give an enolate, which then attacked another molecule of the same ketone.

• The ketones are different from each other.
• Care must be taken to avoid generating many different products.

• You can't really tell which ketone will be converted into the enolate.
• There will be more than one type of enolate and more than one type of ketone present.
• There are a number of possible reactions that can happen, and this will result in a mixture of products.

• It is important to avoid these types of situations.
• There is a very easy way to avoid this issue.
• If there is no alpha protons in one of the ketones, it cannot form an enolate.

• The compound has no alpha protons.
• It can't be converted into anolate.

• One way to cross aldol is to make sure that one of the reagents has no alpha protons.
• The number of potential products will be minimized.
• If both starting ketones have alpha protons, your textbook may or may not show methods for crossing aldol.
• If you are responsible for such methods, you should look through your textbook and lecture notes.

• The method we used before can be used again.
• We need to do it in a different way.
• We break the molecule apart to get water.

• We have to decide which fragment has the oxygen atom and which fragment has the protons.
• The fragment on the left has a carbonyl group, so it must get the two alpha protons.