In this video, I want to give you guys an overview of 3 separate reactions that all do the same thing. What they do is that they alkylate the alpha carbon of a carbonyl. Let's get started. Adding R groups to alpha carbons turns out to be very important synthetically. There are a lot of reasons that we would want to add an R group to an alpha carbon. It turns out that if we want to do that, we're not limited by techniques. There are actually 3 different things, 3 different reactions that all do this. I'll just write down the number 3. I'm going to go through these 3 synthetic pathways now, all in order so that you guys can get an idea of how they all work together. But your textbook might not teach them all in this order. I personally think that's a mistake. I think your authors made a mistake if they didn't teach them back to back because they all do the same thing. But for right now, I'm just going to give you this overview and then we'll just take every reaction as it comes in your textbook. Every chapter that it's in, then I'll do that reaction. But just keep this in mind that they're all really doing the same thing.
The first method is direct enolate alkylation. Enolate alkylation just says that I'm going to use a base to form an enolate and that enolate is then going to attack an alkyl halide. Then I would do like a backside attack and I'm going to get an R group on that enolate. Of course, we'll talk more about this in the actual page about enolate alkylation. One thing to keep in mind is that pretty much anytime that I tell you that you can alkylate something, it means that you can also acylate something. To acylate something, that means that you'd be using an acid chloride. The mechanism would be extremely similar. It would just be that your negative attacks the carbon and eventually, you kick out the Cl. It means that you'd get a carbonyl there instead of just an R group. But this is the first reaction that does alpha carbon alkylations and it's called enolate alkylation. It's definitely the most straightforward of the 3.
The second one is called enamine alkylation or enamine alkylation. You guys should be approaching the point where you learn about enamines and how to make enol enamines. Enamines are when we add a secondary amine to a carbonyl in an acid-catalyzed environment. What an enamine does is it makes we're going to go through this, of course, separately but it makes a molecule that looks like this. We have a double bond, an N with 2 R groups. It turns out that enamines are also great nucleophiles at the alpha carbon. Enamines can also do backside attacks on alkyl halides and they can also add R groups. You might be wondering what happens to the nitrogen. It gets hydrolyzed. Don't worry. There's a whole acid workup and you get rid of it. But we'll talk about it. But in the meantime, just know that it does the same thing. In the same way, you could also react with an acid chloride. An acid chloride would just do an enamine acylation. That was the second way. Obviously, it's more steps. You can see it's 3 steps. But the reason that it's so many steps is because the first step is to make the enamine. The last step is to hydrolyze the enamine. The middle step is the actual electrophile that we react with. Really, this is very similar to enolate alkylation. It's just that you have to do that first step and that second step.
Finally, we get to the last one which is acetoacetic ester and dicarbonyl ester alkylations. With dicarbonyl ester alkylations, what we do is we end up forming an enolate between the carbonyls because we know that is the most stable place for an enolate to form because it has the most resonance structures, that's the most acidic proton. That negative charge ends up doing an SN2 attack and adding an R group in that location. We go through a complicated process where then we hydrolyze the ester and decarboxylate it to remove that entire species and then we're left with the same exact thing that we started off with the other two reactions which is just an alpha-alkylated carbonyl. This one obviously looks like it's the most complicated because now we have 4 reagents. But really guys, it's a synthetic pathway that once you learn it, you're going to get so good at it. It's not even going to matter. You're going to be like pros at this. Again, these three reactions, I might not teach them to you in perfect order from here on out. That's going to be because I'm going to try to follow your textbook as closely as I can. Sometimes, your textbook will split this up between 2 different chapters and that means that I'm going to have to split up the explanations in 2 different chapters as well. But I want you to always refer back to this page so you can understand to yourself that these three reactions are related to each other very much so that they do the same exact thing just in different ways. That being said, let's move on to the first reaction.
