Ch. 21 - Enolate Chemistry: Reactions at the Alpha-Carbon WorksheetSee all chapters
All Chapters
Ch. 1 - A Review of General Chemistry
Ch. 2 - Molecular Representations
Ch. 3 - Acids and Bases
Ch. 4 - Alkanes and Cycloalkanes
Ch. 5 - Chirality
Ch. 6 - Thermodynamics and Kinetics
Ch. 7 - Substitution Reactions
Ch. 8 - Elimination Reactions
Ch. 9 - Alkenes and Alkynes
Ch. 10 - Addition Reactions
Ch. 11 - Radical Reactions
Ch. 12 - Alcohols, Ethers, Epoxides and Thiols
Ch. 13 - Alcohols and Carbonyl Compounds
Ch. 14 - Synthetic Techniques
Ch. 15 - Analytical Techniques: IR, NMR, Mass Spect
Ch. 16 - Conjugated Systems
Ch. 17 - Aromaticity
Ch. 18 - Reactions of Aromatics: EAS and Beyond
Ch. 19 - Aldehydes and Ketones: Nucleophilic Addition
Ch. 20 - Carboxylic Acid Derivatives: NAS
Ch. 21 - Enolate Chemistry: Reactions at the Alpha-Carbon
Ch. 22 - Condensation Chemistry
Ch. 23 - Amines
Ch. 24 - Carbohydrates
Ch. 25 - Phenols
Ch. 26 - Amino Acids, Peptides, and Proteins

Concept #1: Formation of Enolates

Transcript

Now we're going to focus on one of the most important intermediates for all of our organic chemistry and that's called the enolates specifically in the base-catalyzed tautomerization mechanism. The base-catalyzed version, we form a resonance stabilized intermediate called an enolate. Let me show you.
Remember that in the base-catalyzed version, what winds up happening is that my O negative grabs the alpha proton right away. I wind up forming a double bond here and then kicking electrons up to the O. This gives me a possible resonance structure though where on the one hand, I have the negative charge on the O but I could easily resonate that down to the carbon, then it could resonate back up. Both of these are considered the enolate anion and both of them are correct. But for the purposes of this section, one of these is going to be far superior in helping us predict what the product would look like. The one that we're going to use is the one where the negative charge rests on the carbon. Why? Because that's going to help us to realize that alpha-carbons in a basic solution are actually good nucleophiles. That's totally different from anything else we’ve done with carbonyls before because up until this point, we've been taking carbonyls and we’ve been saying that they're good electrophiles, that it's good to add stuff here.
But now what I'm telling you is that the alpha-carbon is actually a good nucleophile, meaning that the alpha-carbon can actually do this. We have a whole new set of reactions; a whole new branch of carbonyl chemistry tree opens up to us when we use enolates.
Now what I want to do is I want to use the next section to compare nucleophilic addition, which is a mechanism you should already be familiar with, with the mechanism of enolates. 

Concept #2: General Reactions

Transcript

So, by now I really hope that you're familiar with nucleophilic addition because it's just that important. Remember, that you've got a partially positive carbon on the carbonyl, nucleophiles can attack it, kick electrons up to the O, I wind up getting a tetrahedral intermediate and remember that at this point that O negative has no other choice other than to protonate because it has no good leaver groups that it can kick out. So, just going to protonate instead and make a substituted alcohol, okay? This is the reaction that grignard's undergo, that reduction undergoes and lots of other negatively charged nucleophiles but what happens if instead of reacting my carbonyl with any random nucleophile, what if I react it with a face, okay? With the base specifically suited to take off an alpha proton, well what's going to happen guys is that you've got an H, right? If you use a base to pull off a proton, what you're going to do is you're going to make an enolate anion, okay? This is a completely new reactive species because now if I have a negative charge on that carbon I can use it to attack random electrophiles, okay? And if I can attack electrophiles with my alpha carbon that means that I'm going to have a way to put things on the Alpha carbon, meaning that the products of these enolate mediated reactions is alpha substituted carbonyls where actually get things on the alpha carbon and that's super important, so guys nucleophilic addition is what we're used to seeing with carbonyls but the new mechanism that we're going to be using in this section is called electrophilic alpha substitution because the fact that you're now attacking electrophiles not nucleophiles, right? And you're now going to be substituting things on the alpha position. Notice that at the beginning I had an H and I ended up with an E, that's going to be the whole theory in this area, when we do with enolates we're going to be using them to substitute hydrogens for whatever electrophile we want to react with, okay? So, awesome, hope that makes sense, that's the general reaction. Now, let's move on to some specific reactions.

Additional Problems
Which one of the following  cannot form an enolate anion? a 2,2-dimethylbutanal b 2-ethylbutanal c 2,3-dimethylbutanal d 3,3-dimethylbutanal e All can form enolate anion
Which of the following compounds exchanges the largest number of hydrogens for deuterium when treated with KOD in D2O? A. 6-methyl-1,4-cycloheptanedione  B. 2-methyl-1,3-cycloheptanedione C. 5-methyl-1,3-cycloheptanedione D. 3-methyl-1,2-cycloheptanedione
Draw cyclohexanone and its enol tautomer. Place the correct symbol between them.
Draw all reasonance forms for the enolate conjugate base that is produced when the compound below is treated with sodium ethoxide. Place the correct symbol between them.
Draw in and circle the most acidic hydrogen (or hydrogens) in each molecule below and place them in order of their acidity with #1 being the most acidic and #4 being the least acidic. 
Which of the following hydrogens is most acidic? Hint: try drawing out the conjugate bases to see which is most stable.
What set of ketone (1) and aldehyde (2) will provide the same alchohol product (3) when submitted to the reaction conditions shown?
Read the following statements and decide whether they are True or False.    1. Enolates are similar to enols but they are for more nucleophilic T or F 2. In order to generate an enolate we we need either an acid or a base to abstract an alpha hydrogen T or F 3. The pka of an alpha hydrogen on a single carbonyl is ~20 T or F 4. The choice of base will determine the extent of enolate formation. T or F
Which base should be used to quantitatively convert this  N,N-dimethylamide into its enolate ion?
Draw the product formed when the following starting material is treated with LDA in THF solution at -78°C. 
Draw the structure(s) of the major organic product(s) of the following reaction.