Conjugate Addition

Concept: Concept: 1,2 vs 1,4 Addition

Video Transcript

Alright guys. So, now I want to take this concept one step further and talk about what happens to enone after it's been reacted, can it keep reacting? turns out it can. So, now we're going to talk about what's called conjugate addition of enones. Remember, that enones are those alpha beta unsaturated products of aldol reactions, okay? Cool. So, guys just before we even get started I want to just give you a disclaimer that this topic is called a lot of different things, it's also called 1,2 vs.1,4 addition of enones, it's also called nucleophilic addition vs. Conjugate addition of carbonyls. So, just letting you know that if you find it in your textbook or online, it's got a lot of different names but it's all the same concept, okay? And, what the concept is, is that once an aldol condensation is completed and you make your enone, right? This is your enone, an electrophilic carbonyl still remains guys, you still have this very partial positive. So, do you think that it has to stop reacting, no guys this can connect again, okay? Not only that not only is it susceptible to nucleophilic attack the way that a normal carbon would be, but now it actually has a second electrophilic region a second reaches, how does that work? because if you look at the resonance structure of this molecule you could always push the electrons up to the O, right? That would give me a positive and a negative, okay? That's just a resonance structure of a carbonyl. Well, another resonance structure would be. Now, that we have this conjugated portion we could move this double bond into here and then I could get the positive up here, that means that I have an electrophilic region at the 2 position, if you consider my oxygen to be 1, okay? Then at the 2 position, I have an electrophilic region. So, I have a 1,2 electrophile, but I also have an electrophilic position at the four, if you're going to consider my oxygen my 1, this would be a 1,4 electrophile, so how do I know if I'm attacking with another nucleophile? how do I know if I'm going to attack the 1,2 or the 1,4, okay? Well, the 1,2 guys is what we call the nucleophilic addition, this is like something you should be extremely familiar with because we've been doing this a lot, nucleophilic addition. Now, the 1,4 addition because it has to do with a conjugated compound that resonated, this is what we call conjugate addition, okay? So, when I say 1,2 versus 1,4, that's the same thing as saying nucleophilic versus conjugate addition, cool? So, guys the answer is it's complicated, it's going to depend on the nucleophiles, okay? So, specific nucleophiles are going to favor the nucleophilic addition, the 1,2, and specific nucleophiles other new proposals going to favor the 1,4, okay? So, let's just hash these out, okay? So, nucleophilic addition is actually going to be the minority of reactions because that conjugate position is very reactive. So, there's really only two reactions that, I know of that are going to want to do this nucleophilic addition on an enone, okay? And, that's going to be, 1, grignard, Oh man I'm creating the N, I'm sorry guys, Grignards, okay? Grignards and 2, organolithium. So, I'm going to put RLI, okay? These are extremely strong nucleophiles that are going to go for this site just like always and we're going to wind up getting a substituted alcohol except that the alcohol happens to have a double bond on it, okay? Conjugate addition is going to be the majority of additions guys. So, pretty much any other nucleophile besides a grignard or an organometallic is going to, or an organolithium, is going to attack here at the fourth spot, okay? And, what I'm giving you here is specific versions of that. So, let's just say you took a generic nucleophile. Well, the product of a generic nucleophile attacking that fourth position would look like this, okay? Notice that there's no more double bond, okay? No more double bond. Alright, it's just going to be in that fourth position, okay? So, guys just so you know some examples of general nucleophiles that could do this would be, I mean, there's a lot of them but specifically CN negative is a very common example, okay? Also a gilman reagent so the R2CLi, that's also called a lithium diorganocopper or gilman reagent. Now, notice that it's easy to confuse this with these guys, but it's different, the lithium diorganocopper, we mentioned before is weaker than a normal organometallic. So, I'm going to expect it to add with my conjugate addition not with my nucleophilic addition and then honestly guys just make something up I mean, there's a lot of different nucleophiles that could react there. Now, to specifically that I want to act this list that are very important are the nucleophiles that are going to make a micro reaction and a stork enamine synthesis, okay? A because it turns out that a micro reaction is going to be a conjugated addition of an enone with an enolate, okay? So, a micro reaction specifically is, when you're using enolate to attack that fourth position, interesting right? So, when you use an emulator to attack the fourth position, you're going to wind up getting even more carbons attached to each other, okay? So, when enolate would be specifically a micro reaction. So, micro reaction is a type of conjugate addition but it's only of enolates, okay? Then, we have stork enamine synthesis, stork enamine synthesis is when you use an enamine, okay? So, remember, what an enamine looks like, let's say a double bond something like this, okay? I'll make it a really flat cyclohexane there, okay? So, when use a stork enamine synthesis, again this can be a nucleophile, you can get electrons going down to the N, it can be a nucleophile and it can attack that fourth position, okay? Now, what is so cool About both of these reactions guys is that both the michael reaction and the stork enamine synthesis make the same exact thing, guys they make 1,5 dicarbonyl, okay? Now, 1,5 dicarbonyl might not sound like they're very special, like why is that so special it's just random carbonyl in different places but if you think about it guys 1,5 dicarbonyl are special for one reason they can cyclize, okay? They can cyclize and self condensate, why? Because they like to form six membered rings, so the rabbit hole is just getting deeper guys because now I'm telling you that the product of an aldol can react with stuff. Now, I'm telling you that the product of an aldol can react with another aldol to make an aldol product that can cyclize through aldol, alright? so obviously there's a lot going on these things can just keep on reacting and reacting and at some point we've gotta call it quit because this could just go on forever but there are a few more reactions that are specifically going to need 1,5 dicarbonyls that I want to teach you because most textbooks or professors don't really put it together, don't explain how the michael reaction and the stork enamine synthesis both really do the same exact thing to get to the 1,5 dicarbonyl. Alright, so other than that. So, you guys understand that your nucleophilic, or yeah, your nucleophilic addition just happens with these two reagents, everything else adds conjugate, let's just add one more, we forgot to put the enamine here, enamine is another one we could use I might and let's just put a random one. So, just you guys can see that it's like everything. So, like, for example, N3 negative, okay? So, any nucleophile first a nucleophile could react at that fourth position and cause that reaction to happen, okay? Cool. So that being said, let's move on to the next video.

Conjugate Addition Additional Practice Problems

Predict and draw the major product of the following reaction.

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When Br2 is added to buta-1,3-diene at -15 °C, the product mixture contains 60% of product A and 40% of product B. When the same reaction takes place at 60 °C, the product ratio is 10% A and 90% B.

(a) Propose structures for products A and B. (Hint: In many cases, an allylic carbocation is more stable than a bromonium ion.)

(b) Propose a mechanism to account for formation of both A and B.

(c) Show why A predominates at 15 °C, but B predominates at 60 °C.

(d) If you had a solution of pure A, and its temperature were raised to 60 °C, what would you expect to happen? Propose a mechanism to support your prediction.

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Complete the following reaction supplying the missing reactant, product or reagent.

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Complete the following reaction supplying the missing product and showing correct regio- and stereochemistry where applicable. If a racemic or diastereomeric mixture forms show all stereoisomers; if no reaction takes place, write N.R.

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Which carbon atoms are most susceptible to nucleophilic attack?

a I and II

b I and III

c I and IV

d II and III

e II and IV

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Draw the reactant of the following reaction. Indicate stereochemistry where appropriate.

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Draw the organic product(s) of the following reaction. Indicate stereochemistry where appropriate. A reasonable answer may be “ No Reaction.”

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