 Well, I designed this talk primarily or totally actually for the nonchemists, so people who maybe have not had organic chemistry or maybe even any chemistry throughout their life. So for some of you, like Chris said, this will be repetitive, and for maybe three of you, it may not be. Okay, so before I get going on this, so I need to start by thanking the people who actually did the work that got me to where I am today. I've had the extreme fortune of working with a number of exceptionally talented graduate students, post-docs and undergraduate students over the years, so they say that you stand on the shoulders of those that come before you. But you also, as a faculty member, the hidden secret is that you get to stand on the shoulders of the people that are in your group at that time also. And so without their dedication and hard work, certainly wouldn't have achieved what we've achieved. That's true of the students that are currently in the group doing the work as well. So I find myself to be extremely fortunate to work with all of you in the third row there. It's an exceptionally nice group, actually a fourth row, sorry, you guys don't count, fourth row. But no, it's an exceptional group of students who are hardworking, who contribute significantly overall to the projects and I appreciate everything you do. Funding, we've been very fortunate to attract funding, well initially from the University of Vermont of course through startup funds as well as some small grants, which I think are very important and I certainly urge the university to continue to supply small grants, particularly to mid-level faculty so they can get new programs up and running. That's been critical. ACS, PRF, AMGEN, NSF and NIH as external funding sources have all been very generous as well. And finally, I'd like to thank my colleagues. I find that this department is an exceptionally nice place to work. People contribute all the time to the success that I've had, whether it be scientifically or mentoring or just providing a nice place to come to work each day and interact. It's a very collegial department and I certainly appreciate that very much. In particular, I'd like to highlight two people. One, Jose, who has, Jose Madalenguadia, who has given me a significant amount of mentoring over the years, whether it be reading research papers before I submit them to journals or reading grants before I submit them and I really credit him with taking the time to do that and I appreciate it very much. The other is Paul Krapchow. Professor Krapchow was my undergraduate research advisor when I was here at UVM and I owe a huge debt of gratitude that I'll never be able to repay to him for taking me under his wing at that time and showing me the beauty of organic chemistry and it really changed my life and got me into synthetic organic chemistry. So thank you, Paul, for that. Okay, so the next slide I'm going to show is a typical organic reaction or maybe I should say a typical reaction to organic chemistry. These are the typical feelings that people have when they first learn that they're going to have to take organic chemistry. So I should, as a qualifier, say that no babies were actually heard in the filming of this talk. This is my daughter and every time we gave her a bath she would make this expression every single time. She doesn't anymore, luckily. However, by the end of the semester, people usually come around and most people end up loving it and even if they don't love it, that might be an overstatement. They usually end up at least appreciating it for what it is and usually end up enjoying it quite a bit. Having said that, this was initially a class of 150 people and these are the people that are left. So not everybody, no, I'm just kidding. This is this year's majors course and so these are all current students and it kind of looks like I photoshopped my head into here, but this is actually my current class. So what is organic chemistry? Well, in the broadest terms, organic chemistry is awesome. It's a lot of fun and I mean this in the two senses of the word. Not only is it just really cool and great, but it's also extremely broadscoped and impacts many different disciplines and impacts everyone on a daily basis even if you don't necessarily know it or appreciate it. More technically, organic chemistry is the scientific study of the preparation properties and function of carbon-based molecules. So I have here the chemist security blanket, which is the periodic table of the elements and as you all probably remember, the elements are what make up everything in the world and then the smallest unit of an element is an atom of that element. And very much like humans, elements get lonely, they don't want to just hang out by themselves and so they tend just like a human to form relationships. Now with humans, those relationships as they're formed, usually you merge resources in the form of a joint bank account, both depositing some money in there with elements, they merge resources in the form of electrons and their bank accounts are bonds and so they both contribute some electrons into bonds. But these aren't your high class name brand Legos, so if you can think of these as like Legos, but these aren't your high class name brand Legos, these are sort of the cheap Legos that your grandparents get you at the dollar store that tend to fall apart all the time when you try and click them together because they happen to be different sizes. So in general, most elements don't form very good bonds to one another and they don't make stable molecules, they tend to fall apart. But carbon is special, right, carbon is special because it forms very strong bonds with other carbon atoms. It also forms strong bonds with nitrogen, oxygen, phosphorus, sulfur, the halogens, as well as hydrogen. And those are the basis of all biological molecules, so they're the basis of life. Are those molecules composed of those elements? Now organic chemists have such a appreciation for carbon that we tend to have a pretty skewed view of the periodic table. And this is a meme I found on the internet which is surprisingly accurate for how an organic chemist actually views the periodic table, right? Carbon is a superstar, you need these to live, hydrogen is carbon's little buddy, and everything else is kind of an afterthought, right? These are named after smart guys, you know, who cares about these things down here. These are probably made up, these are important because they let you do real chemistry with carbon. And everything else is just kind of weird stuff. So, all right, but I was going to take a second now to discuss how organic chemists communicate to one another. All right, so in order for you to sort of understand the rest of the talk, at least when it comes time to talk about structures, you have to have a little background here. So there's really three ways that organic chemists communicate with one another in terms of talking about molecules. The first and simplest is the Michael formula. The second is some kind of name, and then the third would be a structural drawing or representation of the structure. The Michael formula actually doesn't give you a huge amount of information, it doesn't give you any information about the structure, it just tells you what elements are present in the molecule. The problem with that is that oftentimes there's many different ways of connecting these molecules together, or these elements together. So C4H10, I've got two different molecules here that are composed of the same elements that are very different. You can connect all the carbons in a linear structure like this, or you can put three carbons in a row with an extra carbon off the middle. Those give you two totally different molecules that have different physical properties, different boiling points, different melting points, different everything, and so they're just different molecules, they're called structural isomers of one another. So Michael formula doesn't tell you much at all. Name. There's been a huge amount of effort over the years that have been putting into developing a system of nomenclature that can uniquely identify any molecule just by naming it. That is the IUPAC nomenclature system, which is the International Union of Pure and Applied Chemists. And I give them a lot of credit for doing that because I find it incredibly boring. So nomenclature is very, for me, just a huge list of rules that you have to try and memorize and names get extremely complicated very quickly if you don't know those rules and even if you do. So nomenclature is very often a necessary evil, but people tend not to communicate verbally by discussing chemical names. And then the last way is through structural formulas. Now there's a couple of different ways of representing molecules, a structural formula in which all of the carbons and hydrogens are explicitly drawn out is one way. Nobody actually does that because it takes much too much time to write all of these things out. Even though you're showing all the bonds and it's very clear it just takes too much time. Another option that often is used is to not actually write in the carbons. So you draw the structure now in kind of a zigzag form here where at each corner is a carbon atom and so in this case we've still filled in all of the hydrogens. Now I should point out that every carbon makes four bonds if it's going to be a stable carbon. So here we've got a carbon with three bonds to hydrogen and one other bond to carbon. Here's a carbon that's got two bonds to other carbons and two bonds to hydrogen. But that's always the case. Carbon always wants to make four bonds. And so with that in mind you can kind of just ignore the hydrogens and just draw a simple structure like this where now you just know that the number of hydrogens that are present on that carbon are going to make it up into a happy carbon. And so here you just assume that you've got one carbon at the end here that's got three hydrogens on it. This carbon has two bonds to other carbons and so it must have two extra hydrogens on it there. And so it makes drawing these structures much quicker and much easier. If you have what's known as a heteroatom which is any atom that's not carbon or hydrogen then you explicitly draw that heteroatom in and you put any hydrogens on it that happen to be present on it. So here's everybody's favorite organic molecule ethanol and you would draw it out like this. And then finally carbon can make multiple bonds with other carbon atoms. It can share more than one pair of electrons and so in that case you would write two lines here to represent the fact that you've got more than one bond between them. And here's a representation of benzene. You've got a carbon that's got two bonds to this carbon. One bond to that carbon so you know that there's one hydrogen that's sticking out on there. Okay so hopefully with that brief introduction to structure drawing you'll have a better, you'll be better able to follow along with the rest of the talk. Okay so why is organic chemistry important? There's two fundamental reasons. The first is that all living things on earth are organic based. Basically a human body is just a big reaction flask with millions of chemical reactions going on all the time and they keep you alive. If it weren't, well, yeah we'll just leave it at that. Organic chemists, the second reason is that organic chemists can make new molecules that just have a huge impact on humanity. I've got some examples of that here. Explosives, I've got listed here in nitroglycerin, trinitrotoluene as TNT. Both of those are extremely important. They've been important because without them it would not have been possible to lay the transcontinental railroad. It also would not have been possible to make the current highway system. So they've made traveling throughout our country possible and transporting goods. There's a lot of advanced materials that are made from organic structures. So Kevlar. Kevlar was invented in the 1960s by a woman chemist at DuPont who discovered it and it is an extremely strong material. You can make nice threads out of it, make fabric out of it that is extremely strong so it's used to make bulletproof vests as well as many other things. And finally plastics, you know, we're out of the bronze age now and we're into the plastic age. Everything around us is made out of plastics. And in some ways that's terrible because they're hard to degrade. They don't biodegrade all that easily and so they tend to persist in the environment for a long time. On the plus side, every time you drop your shampoo bottle in the shower, you're probably pretty glad that it's not made out of glass, right? So, you know, pros and cons here. What I've drawn here is polystyrene. When you mix polystyrene with air bubbles, you get styrofoam. It keeps your coffee warm. So another benefit, I guess, in it. If that hasn't convinced you about the importance of organic chemistry, maybe this well, most medicines are organic molecules. I can actually only think of one, maybe two medicines that are not organic molecules. So these two here, I'm sure everyone has benefited from aspirin, which is an amazingly simple structure, and amoxicillin. Amoxicillin is a derivative of penicillin. It's one of the beta-lactam antibiotics. This four-membered ring here with a nitrogen and a carbon double bond with an oxygen is known as a beta-lactam, and there's a series of those, which are all antibiotics, and they've saved millions of lives since their discovery. Indenivir is a molecule that has been, was developed as an antiretroviral for the treatment of HIV. It's part of the, one of the cocktail, part of the cocktail combination therapy that has converted HIV from being a terminal illness to something that's manageable for quite a long time. And then finally, Pixantrone here is a cancer chemotherapeutic, and I highlight Pixantrone that there's many different cancer drugs on the market, right? And I could have chosen any number of examples. I've chosen Pixantrone because many of you probably don't realize this, but it was developed right here on UVM campuses by Paul Krapchow, along with Miles Hacker, who was in the pharmacology department at the time. Miles Hacker unfortunately passed away several years ago. But it was actually on this project that I first started working in an organic lab. I never actually made Pixantrone, unfortunately, so I'm not getting any royalties, but I did work on the project and it was a great experience. Thank you. So this collaboration started with support from the Vermont Cancer Center, Borenger, Menelheim, Italia took note and started a collaboration with Krapchow and Hacker. And they produced hundreds of structural analogs. They were all patented in Borenger, licensed them. Eventually, this was finally made to market in 2012 as a treatment for non-Hodgkin's lymphoma. It's currently approved in 15 countries and UVM's receiving royalties from it. So that is an incredibly significant accomplishment. It's really not common at all for a drug to come out of an academic lab. And I think that this should be celebrated and appreciated much more. Okay, so like I said, all biological systems are based on organic molecules. These are the building blocks of DNA, nucleic acids, DNA and RNA. These are based on a sugar background with some phosphates and these are the base pairs that are linked together through non-covalent just hydrogen bonding interactions where these atoms form hydrogen bonds with a share of hydrogen atom basically. And that allows them to link up into these nice ladder type structures. The amino acids, you've probably all heard of amino acids before. Amino acids are also very important in biology. Amino acids are what make up proteins and peptides. So if you link them together, you end up with short chains. These are called peptides. When you make longer chains of them, they end up starting to be called proteins. I think the cutoff is somewhere around, I think it's based on weight actually. And I'm not sure why there's, I don't think there's a really firm number here, but it's usually like a hundred residues or something and peptide suddenly becomes a protein. And these proteins tend to organize themselves into well-defined shapes which are often shown as these pretty ribbon diagrams that biologists and biochemists show. As they get even bigger, you end up forming, sometimes they end up having some kind of function. So this is botulism neurotoxin F. It is an enzyme. These enzymes are little molecular machines that have some kind of function in the human body. But again, all of these are just amino acids that are linked together. There's probably several hundred amino acids, if not more here, then end up making this huge molecular structure that can then start doing some kind of job. Botulism neurotoxin F is interesting for two reasons. One, it's a medicine, so it's a biologic, and it is used for the treatment of eye dystonias. These are muscle constructions of the eye. It was found to be an excellent medicine for that, and it relaxes the muscle so well that cosmetics started to take it over and use it to inject into your face to relieve wrinkles. So this is what you get in a Botox injection. The other thing that's interesting about botulism neurotoxin F is that it's the most potent toxin known to humankind. The LD50, which is the lethal dose at which 50% of subjects die, is 0.3 nanograms. That's 10 to the minus 9 grams per kilogram. So we're talking incredibly lethal. But having said that, I don't think anyone's ever died from an overdose of a Botox injection. So it's very safe to use. It just has to be done in a controlled way. OK, so organic chemistry clearly has its fingers in a lot of different pies here. The one common thing that links all of these together, I guess the one that I haven't mentioned, is natural products total synthesis. So natural products are molecules that are found in nature, and natural products total synthesis is the scientific endeavor of trying to recreate those natural products in lab, re-synthesizing them from scratch. Why would you want to do that? One reason is because most often natural products have some kind of medicinal use. If you think about nature, many plants don't have very many good defense systems against predators. So over the years, they've evolved to generate chemical warfare as their defense. Many plants and small animals will develop toxins, and those toxins can often be used medicinally as well, as long as they're done in a controlled dosage, just like I've mentioned with botulism neurotoxin. One common thing that links all of these diverse areas together, though, is the need to be able to prepare new molecules in order to advance those fields. And in order to do that, people need to develop ways to prepare new molecules. So that's methodology development, coming up with new reactions that will allow you to make new molecules in more efficient or better ways. And my group focuses primarily on methodology development, where we try and develop new chemical reactions. We then apply those reactions in the synthesis of natural products. And we also do a little bit of medicinal chemistry, which is a collaborative project going on between myself, Jianning Li, and the chemistry department, as well as Victor May in neurological sciences. And we're looking to develop some anti-anxiety medications, hopefully for relieving PTSD, as well as other anxiety disorders. But primarily, what we do is methodology development. All right, so organic chemistry in the olden days was classified, or molecules were classified either as inorganic or organic, depending on how they responded when heated. This is back in the 1800s, when you didn't have a lot of good analytical techniques. Nobody really knew anything about structure or bonding or function. No one knew really what they were working with. So inorganic compounds were recovered unchanged when they were heated up. Organic compounds were transformed by heat. So it's the general classification that people used at the time. The going theory was that organic compounds could only be formed by living things. And that through that process, they retained some of the maker's vital force. And when you burned an organic compound or charred it, it was the loss of that essence of life out of the molecule. And that sounds a little hokey by today's standards. But actually, I think from the common, from the general public, probably still believes that without even really recognizing that they believe it. If you were to poll the general public and ask them, would you, do you think a vitamin that is isolated from an orange is better for you than a vitamin that was synthesized in the lab through, you know, from petroleum distillates? Which one would you rather take? Pretty much everyone would probably say the vitamin that was isolated from an orange. But they're identical. There's no difference between the two. They're just an organic molecule. So there's still some, you know, residual thinking here that there's something special about nature. But remember, nature's trying to kill you, right? I got botulism nototox, and that's natural. I wouldn't want to take that. There's lots of things out there that are very harmful. So nature's not always good. Natural's not always better. Okay. Then in the early 1800s, 1828, Frederick Waller, is that how I pronounced it? Is that correct? Yes. Waller? Wolfgang Waller? Okay. Okay. Frederick Waller synthesized the first organic compound in the lab. He made urea. Urea is a fairly simple organic compound, but it is an organic compound by that original definition of something that would be charred when heated. And he was able to prepare it from inorganic starting materials, silver isocyanate and ammonium chloride. And he wasn't trying to prepare urea. He was trying to do something else, but urea is what came out of this. So he said, ureka, urea. And that was really the beginning of organic chemistry. It was the first time anybody had prepared an organic molecule in the lab. Things have come a long way over the years, and we can now prepare just impossibly complicated structures, things like Brevetoxin B, Taxol. These are incredibly complicated molecules that chemists now are able to prepare. But organic chemistry has kind of done itself a disservice in its hubris and its bragging. About being able to make these compounds because everybody assumes, oh, organic chemistry can do anything. Now there's no point in putting any new money into it because it's already a solved problem. But these compounds are not easy to make. It took 123 steps and probably about 300 PhDs in order to prepare this. The final year old was 9 times 10 to the minus 6 percent. That's trace quantities at best. Taxol, 51 steps, .03 percent yield. Taxol is actually a very useful medicine. It's an anti-cancer agent that's used to treat many different kinds of cancers. And the only reason that it is possible to use it as a cancer chemotherapeutic is because a late-stage compound that's very similar to this can be isolated from leaves. And just in two or three synthetic steps you can turn that into the medicine. If you ever had to make it in the lab from scratch, there's no way you could turn that into a drug. And so synthetic organic chemistry still has a long way to go. We've made remarkable achievements, but there's certainly a lot that can be done to improve our standing. And a lot has been done over the years. We've made great advancements, and I've shown here a number of different classic transformations that are very important. Many of which received the Nobel Prize in chemistry over the years. The Aldol condensation didn't, but that's probably because the Nobel Prize wasn't around back then. It certainly would have otherwise. Now the one thing that's in common about all of these transformations is that they start from starting materials where there's two different what we'll call functional groups. Functional groups are not just simple carbon-hydrogen bonds, but functional groups are something else going on, either a carbon-oxygen double bond or a carbon-carbon double bond. All of these transformations take advantage of two different types of functional groups that can react together and come together. The cutting edge now in synthetic organic chemistry is developing reactions that involve only one functional group, and the other being a unreactive CH bond, and being able to conduct a reaction that forms a new carbon-carbon bond or carbon-hetero-atom bond, whatever, but starting with a carbon-hydrogen simple unreactive starting material. A lot of effort's been put into this recently, and I'll show one example from our group where we're able to do this type of transformation in a good way. For the second half of my talk, I will focus on the research that we do. So we've been focusing on studying two synthetic intermediates. One is destabilized vinyl cations, a cation as a carbon. Remember I said all carbons want four bonds, a cation, or at least a carbocation, only has three bonds to it and a positive charge because it's missing a pair of electrons. So we've been studying the reactivity of destabilized vinyl cations, a vinyl cation as a cation that's on a double bond. And what we've found is that we can use these to good advantage in order to prepare pretty complicated molecules and pretty concisely. Just in three steps from a much simpler starting material, we can convert this into a much more complicated and useful product. Intermediate of vinyl cation, we've also found in two steps, we can convert this again from a very simple compound now into a bicyclic structure that's got an alkene present in it. That can be very useful as a synthetic intermediate for other types of reactivity to build off of these kinds of structures. The other project that's ongoing in my group at this point is studying the reactivity of one aza to azona allene salts. Again, that's why nomenclature is the pits. We've discovered that these types of species can react in four or five different reactions depending on what the r-groups. Those r-groups are just variables that you put there just to say it's something just like an x in a mathematical equation. So anyhow, these groups are variable and depending on what they are, you can get four or five different kinds of reactivities out of these intermediates and we've studied all of those reactivities. But what I want to focus on today is just the chemistry of these vinyl cations. This all started totally serendipitously. It actually started from a failed reaction. We were trying to convert this starting material which I'll call a beta hydroxy alpha diazo ester. This is an ester functional group, this is a diazo functional group, this is a hydroxyl group. What we were hoping to do was prepare this kind of scaffold, which you would call a ketofurane, that would have an all carbon quaternary center. So the forming a carbam that's got four extra carbons on it is kind of difficult to do a lot of times and so we were hoping that this would be a way of doing that. Well, unfortunately, we did not get any of that product out of the reaction at all, but I give my graduate student of the time, Christian Dragiccio, a lot of credit because what he did was isolated all of the different compounds that he did get out of that reaction mixture and one of the ones that he isolated was this much more simple structure where now we've got a carbon-carbon triple bond. So if we map out here right along this root, this set of atoms here is what is left over in this structure. What we've lost is the OH, we've lost the N2, but we've also lost this whole chain and we've broken that carbon-carbon bond, somehow we've lost that carbon as well. And so when we saw this, we recognized this as a potentially useful transformation as a way of breaking those carbon-carbon bonds, so we asked how that might happen and we looked back through the literature and there is one example where people had studied similar systems in the past and they proposed that perhaps it had gone through a carbocation. So in our sequence, this is not the reaction that they had studied, this is the reaction that we studied, in our sequence what we think is going on is that the oxygen is getting stripped out of the molecule by coordination to a Lewis acid, which is a metal that can coordinate to things like oxygen. Loss of that oxygen would give what we call a vinyl diazonium, N2 is an incredibly good leaving group, it wants to take off into a gas, N2 is what makes up what, 80 or 90 percent of our atmosphere, so it wants to be liberated. So it leaves and you generate a vinyl cation. At this point, you can break that carbon-carbon bond donating those electrons to that cation to give the triple bond and we've broken that bond and broken the molecule into two different fragments. So we were wondering if we were to do this in a cyclic system, could we break that central carbon-carbon bond? And the answer is yes, that works very well. If we start with what we're calling now a gamma-siloxy, beta-hydroxy-alpha-diazoster, which again is kind of a mouthful but they're actually quite easy to make, if we treat those with a Lewis acid, which in this case is a metal that wants to coordinate to that oxygen. We do end up indeed breaking that carbon-carbon bond. We end up getting a new molecule out. Okay, the next step when you're doing synthetic methodology is to show that this isn't just a fluke in that it works again in other systems. So we did a theroscope study and made a whole bunch of different examples that show yes, this is a general process, it works well all the time. And then in fact, we also found that if we start with a bicyclic system here where that bond that is the ring fusion point, that bond is the one that breaks. We can make these large ring systems or medium ring systems that have an alkyne present in them and those are kind of interesting and useful compounds as well. All right, so who cares? Why is this useful or important? Making these kind of compounds that have two different functional groups present in them, there's a lot of different ways that you could take advantage of these two different functional groups as a synthetic intermediate and this is a pretty simple and easy way to make this compound. The way that we've been taking advantage of these is through another set of reactions that ends up forming now a new five-membered ring that contains nitrogen. So this is a nitrogen heterocycle. It's called a 2,5-dihydropyryl for people that like nomenclature. And these are formed very easily in one step just by treating this with one of the 20 natural amino acids. If you heat them up together, you end up getting what's called an azomethine illid that can react with the alkyne that's across the ring there, that triple bond, and you end up forming the two new bonds here that are shown in red. All right, so that's a pretty quick way now of going from a very simple material to something that's much more complicated. All right, but again, who cares? Why would you want to make these kinds of compounds? Well, it turns out that they're pretty prevalent in a lot of alkaloid natural products, and alkaloids are compounds that are found in nature that contain a nitrogen within one of the rings. So we've used this methodology as a way to prepare two different natural products, demycidine and cyclo-clavine. Those are natural products found in nature or molecules that are found in nature. This tricyclic portion of aspitospermidine, we've also prepared. We have not yet put on this yellow fragment, but we have thoughts on how to do that. Okay, so these are several of the natural products that we've made in our group based on this kind of reactivity. More recently, we've been looking to take advantage of these vinyl cations in other ways. The CH insertion methodology comes into play. I found an old report in the literature which interestingly was only cited, I think, eight times. All right, so it has been not received very much attention at all, but I was surprised at that because it's a very interesting transformation. What they found was if they take an alkyne and treat it with, this is called an acid chloride, it's a way of generating a vinyl cation, but that's not terribly interesting. The interesting part is that that vinyl cation can then react with a CH bond from a far away methyl group to form a new carbon-carbon bond in the course of that reaction. This is a CH insertion reaction where we're taking a non-reactive, unfunctionalized carbon CH bond and turning it into a new carbon-carbon bond which is much more useful and worthwhile. We started thinking, if we were to start with a similar substance, a beta-hydroxy-alpha-diazo, in this case a ketone rather than ester, and we're missing this other OH group out here, so that if there was an OH there, we'd expect to get the ring to fragment. Without that OH, we're hoping the ring won't fragment, and what we're hoping is going to happen is we're going to end up with a vinyl cation. This vinyl cation is called a destabilized vinyl cation. It doesn't want to be sitting right next to this carbon-oxygen double bond, for reasons I won't get into. This destabilized vinyl cation should become a more stable vinyl cation through a bond migration, so this carbon-carbon bond jumps over to there, giving you now a seven-membered ring from what was a six-membered ring. Now we're set up to hopefully do this insertion reaction where we can generate a new carbon-carbon bond between those positions and get now a bicyclic system that has an alkene present and we've got this new carbon-carbon bond that was formed over this process. It turns out that this works really quite well. If we start with this diazo-starting material, we get 83% yield of this insertion product. That's where our chemistry stands right now. This work was done by Sarah Cleary and Magenta Hensinger, who have been developing this methodology but hope to have a paper out on it within the next month, if not sooner. There are other people in the group who are also working on similar, well, not similar, but taking advantage of vinyl cations in other ways. John Fang and Nick Dodge have been working on that chemistry to take advantage of these vinyl cations in different ways. With that, I will conclude my talk. What I hope I have convinced you that organic chemistry is a worthwhile pursuit. There's some real elegance and beauty in natural product total synthesis, which I haven't really had a chance to highlight, but it's really an artistic and creative endeavor that can lead to very useful and worthwhile things. Thanks again to the people that I work with. It's been a real honor and pleasure to work with all of you and thank you very much.