Moving Functionality - Video Tutorials & Practice Problems

Moving Functionality in Synthesis

the synthetic cheat sheet talked a lot about moving functionality from one atom to another. And that's what I want to focus on in this page. I just want to focus on some practice problems of figuring out which direction to go and how to move these things in real life. Okay, so this chart is the same exact one from the cheat sheet. But let's go ahead and fill it in really quick. So remember that Let's do our eliminations first. What kind of base would be favored for sites of elimination? Small and strong. Okay. And then for a Hoffman, it'll be poking. Remember that. Okay, then for the Markov Nankov alcohol. Markov Makov. Um, al Kyohei lied. The alcohol, It was easy. That would just be h x. Okay. From a Kalashnikov alcohol, the one that we usually use is just h a over h Okay, but we can also use Oxy. Mark, I'm just going to write it down, okay? We can also use oxen work if we want thio. Okay, then, for the anti marks, it was the same deal. But I have to use hbr specifically over peroxide. Okay? And for on for my alcohol from my answer Mark alcohol. I would want to use Hyderabad oration. Okay, I'm just gonna write hydro operation here because you guys are such pros at Hyderabad oration already. I'm just gonna right here Ph three. Cool. So now we know kind of our roadmap. And then remember, we said that if you start off with a alcohol, you need to do a new elimination first. If you start off with a double bond, you need to do in addition first, cause it doesn't make sense. You can't add to something that's already added. You can't eliminate something that's already eliminated, so you have to alternate. Okay, so that's what it's just us up here. So what I want you guys to do for these practice problems is first of all, the most important thing, honestly, is just identifying which direction do we want to go in? Because that's something that a lot of students aren't used to doing on. That's not something that professors really teach. So for problem a go ahead and pause the video and just tell me, like, is this gonna want to go in the more substituted direction or in a less substituted direction from that chlorine to that alcohol. Okay, So literally pause the video. And then when you're done, Tommy, if it's gonna be in the more stupid or less. All right. So I hope that you said that it's going in the more substituted direction. Okay. Why? Because notice that I'm starting off with a primary and I'm ending up with a tertiary. That's all you need to dio. That means I'm going in the more substituted direction. Okay, so for B, what direction am I going? Well, it's the opposite, right? So I'm going from tertiary to primary, so this would be in the less substituted direction. Does this give us a clue about what re agents we should be using here? Yeah, it does, because it's like we have our whole blueprint right here. First of all, I know that I'm going for this red one A. I know I should be going in the more substituted direction, so I know I should be using the regions from the top of my chart. I should be using either my decisive elimination or my Markov knock off editions. Cool. So far. On top of that, I'm starting off with an alcohol. So since I'm starting off with an alcohol, which one should I start with addition or elimination? I should start off with elimination. So check that out. It's telling me exactly what to do. I should use a small, strong base to do a sites of elimination from my first step. Isn't that crazy? Because that's gonna lead me to the to the more stable product. Thio. I mean to the one that's more substituted. Isn't that crazy? So I just want to show us how it's like a road map like this is such an awesome chart. Let's keep going. So So why don't we do the first one together? Since, you know, this is just really good practice, and I think it helps if you guys were listening to the way that I think about it. Okay, so we just said that for my first step, I should use a small, strong base that's a decisive base. So let's go ahead. And, um, in this case, I actually don't have the choice. Between sites. Even often notice that I only have one elimination product possible, and that's this. Don't want it there, so I should just do whatever is going to give me the highest. The most amount of elimination product, not the most sites it. Okay, So what that means is that I should actually use a bulky base because my small bases might do in s into Okay. For example, um, oxides oxides will do an s and two if its primary. So let's actually just use L d. A. For my first step. Okay, So what that's going to do is that's gonna give me a molecule. It looks like this. Okay, Snow, I have that. So, now, um, I still trying to go in the more substituted direction? Yeah. I'm still trying to go towards that tertiary, so I should still be looking at the top of my chart. Okay. I should be looking at the more substituted direction right now. Okay, let me make it in red. Okay. So I should be going in, the more substituted. And since I'm starting with a dull bond now, should I use addition or elimination? I should use addition. Okay, So it's really up to you guys. Which one you want to choose? Okay, but I would prefer to pick, unless you can't have car market and shifts at all, which happens sometimes. Let's just pick H x. Okay, because h x actually can shift, and it's easy to eliminate. Okay, so let's go ahead and just use HBR. Okay? Now, if you couldn't shift at all, then you should use instead of a checks you should use Oxy, Mark Oxy Mark is this is the one that you choose when you can't shift at all. So what that's going to give me now is it's going to give me a car. Broke a tie in here. That's then going to shift through. Ah hydride shift Thio here. So we're going to get at the end of this step isn't gonna wind up getting a br right there. Okay, cool. So I've got a br okay and trying to figure out how to make that into this. Okay? Do I have a one step way to do that? So I have one step away to take that br and make it into a Ohh. Well, maybe what you're thinking is s n two. Okay, remember that s and two reactions could swap out Malkiel Hey, lied and put something else there But Actually, that's not a great strategy on the reason is, because s and two can't work on a tertiary. Okay, So really, the best thing to do here is actually, just let's eliminate. And then let's add the alcohol. Okay, Um, so let's go ahead and go ahead and do that. So what we would do is we would we could do any elimination we want because we're just trying to get that Markov Nick. Aww. Site. So we could just use any more cosmic off base like any Ohh for tertiary. And what that's going to give me is a dog. One looks like this once, Okay? It's not with the old one that looks like that. And then I could use an acid catalyzed hydration to do my last step so I could use basically h two s over h 20 And that would give me the last step. Um, our cosmic off alcohol right in the middle. Okay, so that was one way to do it. Notice that the amount of regions that I used was l d a h b r n a O h and then h two s 04 over h 20 not terrible. We did it in four. Okay, I'm going to write that down. Just let us have it. We had HBR then we had on anyway. H And then finally we had h two s over h 20 Okay, so that was a decent synthesis. Was there faster way to do it. Actually, there, Waas. There was a faster way to do this. And I wanted to see if you guys would see it or not. Okay. Ah, faster way to do this would have been and both are right. One of them is better, though. Would have been Yeah, I'll do L d a. From the very beginning. Okay? And that would still give me the stole bond here. Okay, But then instead of doing HBR at the end, what I wanted was an alcohol anyway. So how about instead of doing HBR? I just did my actually catalyzed hydration, so I did a choice of four and water. Okay. And what you'll notice is that well, that gives you you know, what does that give you? Well, that's going to give you a car. Will cut in here. And that's going to shift because of ah hydride Thio here. So I'm gonna wind up getting a carbon cat in here, and then that's when my water attacks. So, actually, my water could have just gotten there in two steps. Okay? I could have just used L d. A. And then h two s 04 over age tool. Okay, so both of them worked. And that's the thing about retro synthesis. Ah, lot of times, you're gonna have several options available to you to get something done. Okay, the better one is gonna be the one that happens in the less steps. So the one that we should really pick is this one. That's the better one. Okay, cool. So I hope that you guys just saw how we can use this flow chart. Basically, that was this flow chart with this, like, kind of like this guide to figure out. Are we going more certitude or less substituted, And then what's kind of our goal? Okay, so now we're gonna go to be, and I want you guys to do this one on your own and figure out how to go from the mawr substituted to the less substituted. So Maybe you should be looking at the other part of the guide, and I'm gonna let you guys try to take care of it, and then I'll answer it for you, so go for it.

Propose a Synthesis

All right. So for this one, um, I'm going the less substituted direction. Okay, but at the very beginning, Okay, I have a new alcohol, so I actually have to do an elimination reaction. And at the very beginning, I actually want to go in the more substituted direction. Okay? The reason is because noticed that if I eliminate this alcohol, Okay, I'm either gonna make a dull bon here. That would be Di substituted. Or I would make a dull bon here. That would be try substituted. Going in the tri subdued direction actually gets me closer to where I need to go, which is the less substituted direction. So what I want to do is actually used, um, or substituted elimination first and then later on, do the less substituted ones. Okay, Now we have one more kink in this, which is that I haven't alcohol. Is alcohol a good leaving group? No, it's not. So you, actually, if some of you guys put like l d a. Don't write this L d. A or Turkey talk side. Those actually won't work on alcohol at all because alcohol isn't a good enough leaving group. So what? We need to do for this first part is, Well, there's a few different things You could convert it to a good leaving group, which is something that we haven't really done a whole lot of. So I'm not gonna do that. But we could do is just We could do an acid catalyzed dehydration. Okay, So my first step, what I could do is just do h two s 04 over h 20 And what that's going to do is that's going to give me a car, broke a tie in here and eliminate this direction in the sights of direction. So what I would get for the first step is something Looks like this. Okay, now, I just want to point out that we can actually add this to our flow chart. Okay? Zits of works, small and strong works if it's starting with an alcohol. Hey, light. But if it's starting with an alcohol, then I actually would want to use I'm gonna put your base. But if it's starting with an alcohol, then I would actually want to use H two s over h 20 okay, because that's going to give me a sites of elimination that actually works on alcohol. Okay, The strong small base on Lee works on alcohol. Hey, lights. Okay, so you just have one more thing to add to your chart. Okay? So now we've got this double bond, and I'm trying to get the Dole bond toe look like to get this chlorine over here. Okay? So my question is, OK, I have a double bond. So should I add next to eliminate next? I have to add. Okay, so I have tow ad. And in this case, should I add Ante Markov Nick off or more Kafelnikov, Should I add to the blue or to the green? I showed it to the green because it's gonna get me closer to where I need to go. So let's go ahead and do a radical hydrology nation and add a BR right here. Okay, That's getting me really close. So now I'm just gonna put here that my re agent was hbr over peroxide. Okay, so now I have in addition, should I do an elimination or another edition? Have to do an elimination? Okay. Well, what kind of elimination do I want to? I want it to be a sites of elimination in blue or Ah, Hoffman, Elimination in red. I want this to be a Hoffman elimination, so I get closer to the C. L. So what free agents can I use for Hoffman elimination? See, now, we're just gonna do anti. You're gonna do, like, less substitute all the way. So I would use a bulky base. Okay, so let's go ahead and use a bulky base. Let's do L D a. That's just like the bulky weights were using a whole lot today. So what that's going to do is that's going to give me it dull bond. Oops. That's gonna give me a dull one that looks like this. And we are Oh, so close. Okay, we're really we're super close. All we need to do is we need to get a chlorine on that position. Now it turns out that Is that is that the more common composition? Anti Marconnet composition? What do you think? That's anti mark again. So what we can uses HBR and peroxide. Now it turns out you might be wondering why not hcl Johnny just put the chlorine right on there. It turns out that this reaction is Onley favorable with HBR, So unfortunately, I can't use HCL. So what that means is that I'm gonna get a regent. Ah, product that's super close to the end product. But it's just gonna look like this and said br Okay, so now that I've got basically the same exact thing do you have to know of a way that I can change that br for a C L I could just do it s n to. So in this case, I could just take the negative charge. Chlorine. So step five would just be c l minus and see. All minus could do a backside attack and kick out the bro mean, And then I would finally get my own product, which would be this. Okay, so I know that's a lot to take in, but I'm just trying to show you guys how grouping re agents by more subdued direction, less of suited direction can really help. Okay, so now I want us to do one on your own. Very similar. Try to figure out the direction. I'm just gonna give you a hint right now. It's both okay. The direction This is like kind of a trick where at some parts, the direction is gonna be more substituted in some parts of the direction is gonna be less substituted. It's your job to figure out what's the easiest way to make this happen. It's actually not a very hard reaction now, do you? It's not that many steps, but go ahead and try to figure it out, and then I'll give you the answer in just a sec.

Propose a Synthesis

All right. So for this first one, we had to eliminate first because we have in addition, product. And it actually doesn't matter which direction, because they're both exactly the same. So I'm just going to do something to eliminate. Let me just use an a o e t. Okay. It's a strong enough base. And what that's gonna induce is a double bond that looks like this. I'm gonna try to draw small. I'm gonna get it sold. One looks like that. Okay, so now that I have any o e t, the next step is Do I want to add or eliminate? I wanna add. Don't wanna add Markov Nick off or anti Markov Nankov more subsided or less? Well, ideally this bro mean noticed that it's on this branch. Right? And that branch is attached to a tertiary carbon. So, ideally, I want to get closer to that tertiary carbon so that I can then get closer to the branch. So since I want to get closer to the tertiary, that would be more Koebnick. Aww. Okay, so what's an easy way toe? Add Markov. Nankov H X. So let's just use h I this time. Okay? what H X is gonna do is it's going to give me a car broke out in here. Let me just draw it out. It's gonna give me a car, Will cut in there, which is then going to shift with a hydride shift. Thio here. And then finally, my I would attack here. So now I've gotten I a dying relatively close to where the BR is. Okay, so now the question is I have my addition. Product. What should I do next? I should eliminate. But at this point, I'm already at the most substituted carbon. And now I'm trying to get a b r on this primary. So am I going, Morse, Do I want to go in the more substituted direction now or less, Which one I want to eliminate in the less substituted direction. Because now I wanna go towards this little edge over here. Okay? Now I want to go this way. So if I want to go in the if I want to eliminate and if I want to go in, the less substituted, that means that I have to use a bulky base. So let's go ahead and use a bulky base since we've been using it all day, Let's just use L D. A. Okay, So what l d is going to give me is that now I'm gonna wind up getting a double bond right here on the edge. Okay? Because that's the least substituted double bond. And now we need to add right. Well, what what do we add? We want out of roaming. Do we want to add it? Markov, Nick over and humor anti McConnell. Cover more comical anti Mark. So in this case, I would use HBR over peroxide. It's And there you have it. We would get our end product. So we just made it in four steps, and that was actually really the best we could dio its's. That was a law that was a long distance to move for just four steps. So we actually really Well, okay, One of the reasons we were able to move so quickly in just four steps from basically moved. How many carbons? 1234 positions. The reason we were able to do that is because the shift helped a lot. The shift helped. Went in the right direction for us. So it saved us a few steps, okay, But I hope that now you guys are getting the feel for this whole addition elimination thing. It's so common. It happens all the time. Thes questions might be a little bit harder than what you're going to see, but still, the whole principle of addition elimination is a big deal. Okay, so let me know if you have any questions, but if not, let's move on.