Moving Functionality

Concept: Concept: Moving Functionality in Synthesis

11m
Video Transcript

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.
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 Zaitsev elimination? Small and strong. And then for a Hofmann? It would be bulky. Remember that? Then for the Markovnikov alcohol, Markovnikov alkyl halide. The alkyl halide is easy. That would just be HX. For Markovnikov alcohol, the one that we usually use is just HA over H2O, but we can also use oxymerc. I'm just going to write it down. We can also use oxymerc if we want to.
Then for the anti-Marks, it was the same deal, but I have to use HBr specifically over peroxides. And for my alcohol, for my anti-Mark alcohol, I would want to use hydroboration. I'm just going to write hydroboration because you guys are such pros at hydroboration. I'm just going to write here BH3.
So now we know kind of our road map and remember we said that if you start off with a alcohol, you need to do an elimination first. If you start off with a double bond, you need to do an addition first because 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. That's what this just says up here.
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. And that's not something that professors really teach.
So for problem (a) go ahead and pause the video and just tell me is this going to want to go in the more substituted direction or in a less substituted direction. From that chlorine to that alcohol. So literally, pause the video and then when you're done, tell me if it's going to be in the more substituted or less.
All right. I hope that you said that it's going in the more substituted direction. 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 do. That means I'm going in the more substituted direction.
So for (b), what direction am I going? Well, it's the opposite. I'm going from tertiary to primary, so this would be in the less substituted direction.
Does this give us a clue about what reagents 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 in – for this red one, (a). I know I should be going in the more substituted direction, so I know I should be using the reagents from the top of my chart. I should be using either my Zaitsev elimination or my Markovnikov's additions. 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 Zaitsev elimination for my first step. Isn't that crazy because that's going to lead me to the more stable product – I mean, to the one that's more substituted. Isn't that crazy?
I just want to show you guys how it's like a roadmap. This is such an awesome chart. Let's keep going. Why don't we do the first one together since this is just really good practice and I think it helps if you guys are listening to the way that I think about it.
We just said that for my first step, I should use a small, strong base, that's a Zaitsev base, so let's go ahead and in this case, I actually don't have the choice between Zaitsev and Hofmann. Notice that I only have one elimination product possible and that's this double bond right there.
So I should just do whatever's going to give me the highest, the most amount of elimination product, not the most Zaitsev. So what that means is that I should actually use a bulky base because my small bases might do an SN2. For example, oxides. Oxides will do an SN2 if it's primary.
Let's actually just use LDA for my first step. What that's going to do is that's going to give me a molecule that looks like this. So now I have that. So now am 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. I should be looking at the more substituted direction right now. Let me make it in red. So I should be going in the more substituted.
Since I'm starting with a double bond now, should I use addition or elimination? I should use addition. It's really up to you guys which one you want to choose. But I would prefer to pick – unless you can't have carbocation shifts at all, which happens sometimes, let's just pick HX because HX actually can shift and it's easy to eliminate.
So let's go ahead and just use HBr. Now if you couldn't shift at all, then you should use instead of HX, you should use oxymerc. Oxymerc 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 carbocation here that's then going to shift through a hydride shift to here. So what I'm going to get at the end of this step is I'm going to wind up getting a Br right there. Cool.
So now I've got a Br and I'm trying to figure out how to make that into this. Do I have a one-step way to do that? Do I have a one-step way to take that Br and make it into an OH? Well, maybe what you're thinking is SN2. Remember that SN2 reactions could swap out an alkyl halide and put something else there. But actually, that's not a great strategy. The reason is because SN2 can't work on a tertiary. Really, the best thing to do here is actually just let's eliminate and then let's add the alcohol.
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 Markovnikov site, so we could just use any Markovnikov base, like NaOH for tertiary. And what that's going to give me is a double bond that looks like this. So now I have a double bond that looks like that. And then I could use an acid-catalyzed hydration to do my last step. So I could use basically H2SO4 over H2O and that would give me my last step, a Markovnikov alcohol. Right in the middle.
That was one way to do it. Notice that the amount of reagents that I used was LDA, HBr, NaOH and then H2SO4 over H2O. Not terrible. We did it in four. I'm going to write that down just so you guys have it. We had HBr. Then we had NaOH. Then finally, we had H2SO4 over H2O.
That was a decent synthesis. Was there a faster way to do it? Actually, there was. There was a faster way to do this and I wanted to see if you guys would see it or not. A faster way to do this – both are right. One of them is better, though. Would have been, yeah, I'll do LDA from the very beginning. And that would still give me this double bond here. 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 acid-catalyzed hydration. So I did H2SO4 and water.
What you'll notice is that, that gives you – what does that give you? Well, that's going to give you a carbocation here and that's going to shift because of a hydride to here. So I'm going to wind up getting a carbocation here and then that's when my water attacks. So actually, my water could have just gotten there in two-steps. I could have just used LDA and the H2SO4 over H2O. So both of them worked.
And that's the thing about retro-synthesis, a lot of times you're going to have several options available to you to get something done. The better one is going to 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. Cool.
I hope that you guys just saw how we can use this flow chart basically – not this flow chart, but kind of like this guide, to figure out are we going more substituted or less substituted and then what's kind of our goal.
So now we're going to go to B and I want you guys to do this one all on your own and figure out how to go from the more substituted to the less substituted, so maybe you should be looking at the other part of the guide. And I'm going to let you guys try to take care of it and then I'll answer it for you. So go for it. 

Moving Functionality Additional Practice Problems

Propose an efficient method of converting 3-methyl-1-butanol into 3-methyl-2-butanol.

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Provide a curved arrow mechanism for the following reaction.

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Provide an efficient multistep synthesis for the conversion of the given starting material into the target molecule shown to the right. You must begin with the given starting organic compound. All Cs that  end up in the target compound must come from the given starting organic compound. For each functional group transformation, give all necessary reagents, solvents, and catalysts; give a structural formula for each organic reactant and the major organic product(s). Show stereochemistry appropriately when necessary. If a mixture of products (for example a mixture of stereoisomers) must be present after a step, assume that you can separate the mixture and take the one needed product forward through the next step.

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Propose a synthetic way to produce the following compound.

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Propose a synthetic way to produce the following compound.

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Propose a synthetic way to produce the following compound.

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Show how you would carry out each of the following reactions. You do   NOT need to draw the mechanisms

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Show how you would carry out each of the following reactions. You do   NOT need to draw the mechanisms 

 

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Provide an efficient multistep synthesis for the following conversion of the given starting compound into the target compound. For this problem, do not give a mechanism with curved arrows. For the synthesis, more than one functional group transformation is required. For each functional group transformation, give all necessary reagents and catalysts and give a structural formula of the organic product. Also give hv and/or heat when necessary. Show stereochemistry appropriately when necessary. 

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Fill in the missing reagents:

 

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