Moving Functionality - Online Tutor, Practice Problems & Exam Prep

Understanding the direction of reactions is crucial in organic synthesis. For Zaitsev eliminations, a small strong base is preferred, while bulky bases favor Hofmann eliminations. Markovnikov additions utilize HX or oxymercuration, whereas anti-Markovnikov reactions require HBr with peroxides. Starting with an alcohol necessitates elimination first, while a double bond requires addition. Recognizing whether to pursue more or less substituted products guides reagent selection, enhancing synthesis efficiency. This strategic approach streamlines complex reactions, allowing for multiple pathways to achieve desired outcomes.

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 Zaitsev elimination? Small and strong. Okay? And then for a Hoffman, it'll be bulky. Remember that? Then, for the Markovnikov alcohol, Markovnikov alkyl halide, the alkyl halide was easy. That would just be HX. Okay. For Markovnikov also use oxymerc. I'm just going to write it down. Okay. We can also use oxymerc if we want to. Okay? Then for the antimarks, it was the same deal, but I have to use HBr specifically over peroxides. K? And for my alcohol, for my anti-mark alcohol, I would want to use hydroboration. K. I'm just going to write hydroboration here because you guys are such pros at hydroboration already. I'm just going to write here BH₃. Cool. So now we know kind of our roadmap, and then remember we said that if you start off with 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. Okay? So that's what it just says 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. 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 a 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, tell me if it's going to be in the more substituted or less. Alright. So, 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 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 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 for this red one, I know I should be going in the more substituted direction, so I know I should be using the reagents from th

Propose a Synthesis

All right. So for this first one, we had to eliminate first because we have an 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 NaOEt. It's a strong enough base. And what that's going to induce is a double bond that looks like this. I'm going to try to draw small. I'm going to get a double bond that looks like that. Okay? So now that I have NaOEt, the next step is do I want to add or eliminate? Do I want to add, do I want to add Markovnikov or anti-Markovnikov? More substituted or less. Well, ideally, this bromine, notice 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 Markovnikov. Okay? So what's an easy way to add Markovnikov? HX. So let's just use HI this time. Okay? W

Here’s what students ask on this topic:

What is the difference between Zaitsev and Hofmann elimination?

Zaitsev and Hofmann eliminations are two types of elimination reactions that differ in the regioselectivity of the product. Zaitsev elimination favors the formation of the more substituted alkene, typically using a small, strong base. In contrast, Hofmann elimination favors the formation of the less substituted alkene and uses a bulky base. The choice of base and the steric hindrance around the leaving group determine which product is favored.

How do you determine whether to use Markovnikov or anti-Markovnikov addition?

To determine whether to use Markovnikov or anti-Markovnikov addition, consider the desired regioselectivity of the product. Markovnikov addition places the electrophile on the more substituted carbon and can be achieved using reagents like HX or oxymercuration. Anti-Markovnikov addition places the electrophile on the less substituted carbon and requires HBr in the presence of peroxides. The choice depends on the specific product you aim to synthesize.

Why is it necessary to perform elimination before addition when starting with an alcohol?

When starting with an alcohol, elimination is necessary before addition because alcohols are not good leaving groups. Converting the alcohol to a double bond via elimination creates a more reactive intermediate that can then undergo addition reactions. This stepwise approach ensures that the functional group transformations proceed efficiently and in the correct order.

What reagents are used for Zaitsev and Hofmann eliminations?

For Zaitsev elimination, a small, strong base such as NaOEt or NaOMe is used to favor the formation of the more substituted alkene. For Hofmann elimination, a bulky base like LDA (lithium diisopropylamide) or t-BuOK (potassium tert-butoxide) is used to favor the formation of the less substituted alkene. The choice of base is crucial for directing the regioselectivity of the elimination reaction.

How do you convert an alkyl halide to an alcohol?

To convert an alkyl halide to an alcohol, you can use a nucleophilic substitution reaction (SN2 or SN1). For primary alkyl halides, an SN2 reaction with a hydroxide ion (OH⁻) is effective. For tertiary alkyl halides, an SN1 reaction can be used, where the halide is replaced by a hydroxide ion. The choice of mechanism depends on the structure of the alkyl halide.