So in lecture 12-4, we're going to look into more of the specifics about how we actually go about performing a Grignard synthesis. This is the last recording for chapter 12. The reactions we're going to look at here are not going to be in as great a detail. We're going to get to that real specific detail in the worksheets that we're going to do in class.
So on this first slide, all we have here is just a list of guidelines for you. For the most part, you can read through these. I just want to give you an idea of what you're going to see in these types of multi-step synthesis problems.
You're going to be given a target molecule, a molecule that you need to synthesize from smaller pieces, and you're going to be told what is available in your stockroom. Since all of these reactions are going to be primarily Grignard reactions, what you want to do is look at your target molecule, find where the alcohol group is, is and put a dot on that because that's going to give you an idea of where the new carbon-carbon bond is going to form. Once you've identified your target molecule as a primary, secondary, or tertiary alcohol, that'll give you some information as to what type of an oxygen-containing compound you need, aldehyde, ketone, ester, or epoxide. And you can look in your stock room to see you have something there that will that will fit your needs if the the target alcohol has is tertiary and it has symmetrical groups on it in other words two of the alkyl groups are the same that's going to tell you you need to use an ester so you're going to then go to your stock room see what you have you may find you have no alcohols or you have no oxygen containing compounds you might need to take something from your stockroom and convert it into an oxygen containing compound first.
You may also see that you have no alkyl halides, which of course you need for a Grignard reaction. So you have to take something in your stockroom and convert it into an appropriate alkyl halide. This will all become more obvious as we do some problems.
And then you carry out the three steps of the Grignard reaction. So in our first example, we're going to look at the application of the Grignard reaction to take a ketone and convert that into a tertiary alcohol. So the approach we're taking would be the approach of, say, a reaction problem, where you're given the reactant, you're given the reagents, and we have to predict what the product looks like.
More specific examples of using the Grignard reaction for multi-step synthesis, we will do those when we get to class. So in the setup, We have our alkyl halide and we have one, two, three steps of the Grignard reaction. A good place to start is to first put a dot on the two carbons that are going to form the new carbon-carbon bond. In other words, the carbon that contains the halogen and the carbon of the oxygen-containing compound.
So I will use a red dot and a black dot to indicate those. So when we want to start drawing the structure of the product, All we have to do is start with those two dots and put a line in between them, where that line represents the new carbon-carbon bond. The rest is pretty easy.
It's a matter of looking at your alkyl bromide and seeing we've got this methyl group. Well, we've got to put a methyl group on the red carbon. And for the black dot, we've got these two methyl groups, and we're going to have the OH of the alcohol product. And that gives you your product.
The dotted line shows us where the new carbon-carbon bond formed, and it's a tertiary alcohol. Ketones will always give you a tertiary alcohol in a Grignard reaction. Example 2. We're going to take an aldehyde and convert that to a secondary alcohol. So using the strategy that we just outlined in the previous slide, why don't you pause the recording and see if you can come up with the structure of this product. Okay, again we start out by putting dots in the appropriate places.
Red dot on the carbon containing the alkyl halide, a black dot on the carbon containing the oxygen. We then draw those two dots, and now we put on all of the functional groups that belong to them. So the red dot, we have to put this methyl on.
For the black dot, we need to put on this hydrogen, this isopropyl group, and the OH. And that gives us our product. Aldehydes give secondary alcohols. In example three, we're going to take an ester and show that that gets converted to a tertiary alcohol.
As I said in the previous lecture, these are a little more interesting because two Grignard reagents are required. So if I put the dots on in the appropriate places, we're going to have two red dots connected to the black dot. The first red dot... kicks out this part of the reactant.
The second red dot pushes the electrons onto the oxygen. Okay, so I accidentally jumped ahead a little bit. So we start out with the black dot connected to two of the red dots.
And now we got to put on the rest of the pieces. Methyl group, one methyl here, one methyl here. And on the black dot, it's only this part.
Okay, this is the part that goes away. We're going to put this propyl groupon and the OH of the alcohol. Esters always give a tertiary alcohol because you're adding two of the alkyl groups from the alkyl halide. Two grignard reagents are adding. The dotted line shows the two new covalent bonds that were formed in this case.
And the final example is going to be The Grignard reaction is using epoxides. Epoxides are the most versatile. They can be converted to a primary, secondary, or a tertiary alcohol, and we need to keep in mind that the Grignard agent will always add to the least substituted carbon of the epoxide.
So here's our example, the same alkyl bromide that we used in the previous three examples, and we have our epoxide. And notice that on the epoxide on this carbon we have two R groups, and as drawn, this would be the least substituted carbon. So our dots are going to go as shown, the red dot on the carbon containing the halogen, the black dot on the least substituted carbon.
So the red dot and the black dot have to come together. They're going to form the new bond. You may want to pause the recording and see if you can come up with what the product will look like. So, hopefully you realize that this methyl group must go on the red dot. This carbon has to be connected to the black dot with the two R groups.
And that carbon, notice that when the Grignard reagent comes into this carbon, it's going to break this bond with those electrons going on the oxygen. So the oxygen won't be on the carbon with the black dot, it's going to be on this one, the adjacent carbon atom. So epoxides, you may want to spend a little more time figuring out what is happening with epoxides, because they can be a little tricky.
Now, what does that tell us in terms of what type of alcohols we're going to get? Well, if the two R groups are both going to be hydrogen atoms, then you get a primary alcohol. If one R group is alkyl and the other hydrogen, you get a secondary alcohol. And if both R groups are alkyl groups, you're going to get a tertiary alcohol.
So epoxides are great. They can be converted in a whole variety of different types of alcohols. So in class, we're going to be looking at additional problems, more specific ones, and also start looking at examples where all you're given is the final target molecule.
and then you have to figure out everything on the left side. So a little bit of reverse thinking compared to the types of reaction problems we've seen in the past. That is the end of chapter 12 and the end of this recording.