Sharpless Epoxidation: Study with Video Lessons, Practice Problems & Examples

The Sharpless Asymmetric Epoxidation is an enantioselective reaction that converts allyl alcohols into epoxides using chiral tartrates. Positive tartrates yield epoxides formed from above the double bond, while negative tartrates result in epoxides formed from below. Meso tartrates do not exhibit optical activity and lead to non-enantioselective outcomes. To predict product orientation, position the alcohol at the bottom right corner of the double bond. This method simplifies understanding the reaction's stereochemistry and enhances accuracy in predicting epoxide formation.

Important Reagents of Sharpless Epoxidation.

So now I want to talk about a form of epoxidation that has some pretty interesting advantages. The name of this reaction is the Sharpless Asymmetric Epoxidation. So the whole point of this reaction is that it's a form of epoxidation that is enantioselective. What that means is that it's going to generate only one of the 2 possible enantiomers in excess. In fact, it's almost going to perfectly select one enantiomer over another. Now, in order to do this, we're going to use some pretty weird molecules, some pretty weird reagents that overall I would just ask you to recognize more than memorize. Okay? Because most professors aren't going to get into the nitty-gritty of memorizing every single letter of these reagents. They just want you to know what this reaction is about. The way this reaction works is that it's going to convert allyl alcohols. That means it's an alcohol that has a CH₂ and then a double bond. Allyl is a position that says that you're next to a double bond, not directly attached to one. And then it's going to generate a certain epoxide based on the type of tartrate that is used. These tartrates are basically functional groups that have different chiral centers. And what you're going to find is that there are 3 different possibilities of types of tartrates that I could use in this reaction. I could use the SS. I could use the RR. We're talking about these chiral centers right here. Both of them are S. That's considered a positive tartrate. And positive, if you remember, if you see a little positive sign inside of brackets, what that's talking about is the optical activity. So what that's saying is that the chiral centers are S and s. When you run it through a polarimeter, it's going to rotate light clockwise. That's what the positive means. Well, the enantiomer of that would mean that both chiral centers are opposite. So if you have an R R tartrate, that's going to be a negative rotation. The reason is that remember that the enantiomer of any chiral center or of any chiral molecule will always have the configuration, the opposite rotation, but of the other configuration. So for example, if it was positive 20 degrees, then it would be a negative 20 degrees rotation with the negative DET. Then finally, we have an r and an S or an S and an r. This is actually a meso DET, so this one would be actually since it's meso, this one would have no optical activity. Oops. I'm just going to write no optical activity. This is going back to our chirality chapter where we talked about meso compounds and how they don't rotate plane polarized light. So it's impossible to assign a plus or a minus to a meso because it's not going to rotate at all. This is interesting. We're talking about chiral centers. You're like, this sounds a lot like chirality. But what does this have to do with the epoxide? Well, it turns out that you can predict the direction that the epoxide is going to form from what type of enantiomer you're using. So it turns out that the positive DET, the positive tartrate, the one that has the positive rotation of light is going to attack from above. It's going to enantioselectively pick the top part of a double bond to add an epoxide. Then we've got the negative one. The negative one is going to be the opposite, so it's going to pick it's going to attack from below. And we would expect the one from below to now form an epoxide below the double bond. So we've got positive is up, negative is down. That's really easy, right? Then we've got meso. What do you think about meso? Well, meso would just be both. The reason that meso is both is because this one would be non-enantioselective. Why? Because it doesn't have a preference of top or bottom, so it's just going to be a 50, 50 percent chance. Okay. So really we don't really care about the meso one so much and we're not going to use that one synthetically. What we're going to use is positive DET and negative DET as our catalysts to form the upwards epoxide and the downwards epoxide.

General reaction of Sharpless Epoxidation.

So now you're probably wondering, Johnny, how does this actually look in a reaction? Well, here's the general reaction. So here, as you'll notice, I have an allyl alcohol. This is my allyl alcohol right here. The reason we call it allyl is because it is next to a double bond. It has a CH2 and then it has an allylic position. That's a position word. We have an allylic alcohol, and when we react it with a peroxide, this is the oxidizing agent. This is what's going to make the oxygen. Then a titanium catalyst. Don't worry too much about the titanium catalyst. You'll just see that there's Ti there. That stands for titanium. There's a titanium catalyst and then we use one of the tartrates, either negative or positive. When you put all those things together, what you're going to wind up getting is the epoxide then I would use a negative tartrate. A negative tartrate is going to attack from the bottom of the double bond and is going to give me my epoxide at the bottom. Now obviously, that means if the epoxide is facing towards the bottom, then my other substituents must be forced up. Right? Cool. So, so far, I know these reagents are super confusing. But really, I'm not asking much from you. I'm not asking you to memorize them. I'm just saying can you remember that the positive tartrate adds from the top, and the negative tartrate adds from the bottom. Is that cool so far?

How to draw and predict a Sharpless Epoxidation.

All right. So now I just want to add one more little twist to it to make sure that you always get these questions right. If you want to make sure that your alcohol is oriented correctly so that you always predict the right product, you always want to draw the alcohol on the bottom right corner of the double bond. Now what you're going to notice is that in some textbooks, they don't use the bottom right corner. Some textbooks, they use the top right corner. Some textbooks, they tell you other directions. But go ahead and use mine just because of the fact that it doesn't matter which corner you use as long as you're consistent and that's going to be the one that translates to the pattern that I told you about working. So if you learn it another way, that's fine. But honestly, most people really don't understand Sharpless epoxidation, so I think this way works really well.

So we always put this is what I'm saying. If you have your alcohol oriented wherever, you always make sure

Here’s what students ask on this topic:

What is Sharpless Asymmetric Epoxidation?

Sharpless Asymmetric Epoxidation is an enantioselective chemical reaction that converts allyl alcohols into epoxides using chiral tartrates. The reaction is highly selective, producing one enantiomer in excess. Positive tartrates yield epoxides formed from above the double bond, while negative tartrates result in epoxides formed from below. Meso tartrates do not exhibit optical activity and lead to non-enantioselective outcomes. This reaction is significant in organic synthesis for its ability to produce enantiomerically pure epoxides.

How does the Sharpless Epoxidation reaction work?

The Sharpless Epoxidation reaction involves the conversion of allyl alcohols into epoxides using a titanium catalyst and chiral tartrates. The allyl alcohol is positioned next to a double bond, and the reaction uses either positive or negative tartrates. Positive tartrates add the epoxide from above the double bond, while negative tartrates add it from below. The reaction is enantioselective, meaning it produces one enantiomer in excess. Meso tartrates, which have no optical activity, result in a non-enantioselective outcome.

What are the reagents used in Sharpless Asymmetric Epoxidation?

The key reagents in Sharpless Asymmetric Epoxidation are allyl alcohols, a titanium catalyst, and chiral tartrates. The tartrates can be either positive (S,S) or negative (R,R), which determine the stereochemistry of the resulting epoxide. A peroxide is also used as the oxidizing agent to form the epoxide. The choice of tartrate influences whether the epoxide forms above or below the double bond.

Why is the orientation of the alcohol important in Sharpless Epoxidation?

The orientation of the alcohol in Sharpless Epoxidation is crucial for predicting the correct stereochemistry of the product. Positioning the alcohol at the bottom right corner of the double bond ensures consistent and accurate predictions. This orientation helps determine whether the epoxide will form above or below the double bond based on the type of tartrate used (positive or negative). Consistency in this orientation simplifies understanding and enhances accuracy in predicting the reaction outcome.

What is the role of chiral tartrates in Sharpless Epoxidation?

Chiral tartrates play a crucial role in Sharpless Epoxidation by determining the stereochemistry of the resulting epoxide. Positive tartrates (S,S) lead to the formation of epoxides from above the double bond, while negative tartrates (R,R) result in epoxides formed from below. Meso tartrates, which have no optical activity, produce non-enantioselective outcomes. The choice of tartrate is essential for achieving the desired enantiomeric excess in the product.