Carbenes and Cyclopropation

Cyclopropanation is the general name for a series of reactions that all produce very similar products by different mechanisms. You may be responsible for one or more of these reactions on your exam, so let’s get into them.

Concept: General properties of cyclopropanation.      

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Video Transcript

In this video, I'm going to introduce a bunch of new addition reactions that all pretty much do the same thing, so I'm going to group them together in a type of reaction called cyclopropanation.
So a cyclopropanation reaction takes place when a double bond encounters either a carbene or a carbenoid. The product from this reaction is really just a cyclopropane. So we literally get the addition of an alkyl group on that double bond and all you're really getting is a methylene group or a CH2.
So you might be wondering, “Johnny, why would a double bond want to react with a methyl group? I mean, I don't remember methyl groups being strong electrophiles.” Well, that's exactly why we need a carbene or a carbenoid because methyls aren't reactive, but carbenes are.
If you recall, carbenes are reactive intermediates not because of their formal charge. If you look, this is an example of a carbene right here. Does it have a formal charge? No, it has a formal charge of zero. So you might think, “This doesn't look reactive to me.” But remember it has a big problem. It violates the octet rule, so even though it doesn't have a formal charge, it wants to have eight octet electrons around it and right now it only has six. It has that lone pair, those two bonds. It's missing two whole electrons, so carbenes are going to be extremely reactive with pretty much everything, including double bonds, which is why they're going to work to make these triangle-shaped products.
What I'm going to do is I'm just going to go one-by-one down the list of all the reagents that can make a cyclopropanation. 

Concept: Reaction with a simple carbene.

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Let's start at the first one, the first example would just be the easiest example possible reacting a Carbene being directly with a double bond, OK? This mechanism is going to look just like our other three our other bridged ion mechanisms that made 3 ring intermediates it's going to be a double bond grabbing the Carbene and then the Carbene grabbing back, this is going to show us that our product is cyclic now whenever you add a ring to another ring, that ring has to be cis because if it was trans you would break the ring by having to straddle both sides of the original ring so I'm just going to go ahead and draw this as a Cis triangle or cis cyclopropane I'm drawing it as going towards the top and then I would draw my methyl groups that were originally there going down, now this is not a chiral molecules so that's my final answer but if I had some kind of asymmetry then I would draw the enantiomers or just the stereo isomer that would be faced the other way, OK? Now one thing to keep in mind about this this is deceptively easy but there's one thing you need to keep in mind these hydrogens could be swapped for any other atom that just likes to have one bond for example halogens I could easily use a carbene that has let's say CBR2, right? If I did that what we need to add to this molecule? You would need to draw those bromine guys so here I'm just going to draw hydrogen since that's what I was using but keep in mind that if it had been bromines or anything else you would have to add them to the tip of the Cyclopropane.

Concept: Reaction with chloroform (CHCl3) and tert-butoxide.

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Alright so now let's move on to the second reaction that does a cycloproponation and I think this one's actually the trickiest one because if you look at these reagents what you'll find is that they look strangely familiar you have this molecule that kind of looks like an Alkyl Halide or a leaving group, you have this molecule that looks like a nucleophile or a base and you might be thinking that this is in the category of substitution or elimination you might think this is a flow chart question remember that flow chart that we used for those types of reactions? Well it's not though because if you recognize that this is not a typical leaving group typically leaving groups should just have one alkyl or one Halide, Sulfonate ester but here I have 3 chlorines that's not usual that would not be a flow chart question so let's go ahead and look at the generation of this carbene so that you guys can see how it works, basically the way this mechanism works is that let's say you've got your carbon and you've got your hydrogen and then you've got your 3 halogens chlorine, OK? What happens is that this is going to react in an acid based reaction with tert butoxide which I'm just going to draw like this, OK? the tert butoxide is going to look at that hydrogen and it's going to extract it because it's a good strong base so we're going to take away that hydrogen, OK? But if we make a bond we have to break a bond now this is the interesting part you haven't really seen many mechanisms that do this but what we're going to do is we're going to actually place the electrons directly on to the carbon, OK? So essentially instead of going bond to bond we're going bond to atom which is fine but now if we make that bond we have to break another bond we have to kick out one of the CLs, OK? so we wind up getting as a product of this is now a carbene what we're going to get is now a carbon with 2CLs and a lone pair does that look familiar? That is my Carbene that I was able to create through the elimination reaction so instead of beta elimination this would be alpha elimination but it's very similar concept notice the 3 arrows and we're basically taking away a hydrogen, OK? We're getting rid of 2 single bonds, OK? So now we've got our Carbene, what happens? The mechanism just takes over like before, these arrow are going to be really ugly I'll erase them in a second but it would just be this and that, OK? Just the same thing now your product guys is going to be the same exact molecule except what? What do we have to be watchful for? This time we have chlorines so add those chlorines do not forget those chlorines guys they're important that points in your exam, OK? Awesome so hopefully that combination made sense.

Concept: Reaction with diazomethane and light or heat.

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So Let's move on to the next so another reagent that creates a Cyclopropenation is called Diazomethane, OK? Now Diazomethane is an interesting structure because first of all you guys haven't seen this yet this is more into organic chemistry 2 but anytime you see like N-N substituent like this, so I'm just going to write it here and N triple bond N and then R, this is called a Diazo group, OK? It's just a functional group, it's a functional group we don't teach in Orgo 1 just because it's kind of beyond the scope of this course but it's something you will see in the future and something that's really interesting about Diazo group guys is that they love to spontaneously dissociate, why? Because notice that you've got this N-N triple bond and I'm not sure if you guys are aware nitrogen gas is like 78 percent of the atmosphere is nitrogen gas, OK? It's an inert it's super stable, OK? I mean it's been around for billions of years literally so nitrogen gas is I'm just going to draw a little squiggly line is N triple bond lone pair lone pair and this Diazo group has a lone pair there so see how close that Diazo is to be nitrogen gas? it's almost nitrogen gas, all it has to do is pick up these electrons take them away and now it takes off into the atmosphere likely to never be reacted again, this thing is going to be like in its nirvana, OK? If it can just take those electrons so guess what allows it to do that? Pretty much any amount of energy if you insert energy into the system in this case in terms of light energy but heat energy could work as well you will give the Diazo just enough of a little punch to grab those electrons take off and set sailing for rest of its happy life, OK? So this Diazomethane when it grabs a little bit a light gets what's going to happen? It's going to grab when a little bit of what is radiated on it it's going to grab these electrons and what are you going to get? You're going to get N2 gas that's gone, OK? And then you're also going to get what? CHH lone pair, OK? That's the other thing guess what's going to happen? Same mechanism guys now you've got your carbene and that carbene can react with a double bond just like before I'm going to erase these arrows but it just does this, OK? So Diazomethane would actually just give me a Cyclopropane nothing fancy about it, OK? Not behaving today, huh? OK perfect. OK guys so see you I'm grouping these all together because they're kind of like they're all doing the same thing just in different ways.

Concept: The Simmons-Smith reaction.

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Finally we have the Simmons smith reaction, OK? So the Simmons smith reaction is the most complicated in terms of your reagents I don't need you to memorize all the different combinations as long as you can possibly remember the bottom one, OK? So the reagents are this, let me just list that out for you, there is Diiodomethane, OK? So that's the first one here so I'm just going to make that one red, there's a Zinc-Copper couple that's this and when you react those two things together guess what happens when you react the Diiodomethane with the Zinc-copper couple you get them to react together to make something called Iodozincmethyl iodide, OK?

Literally exactly the way it looks is the way you state the name and this is what we call the Simmons-Smith reagent, OK? So the Simmons Smith reagent would be this guy right here, OK? Now that looks really complicated but see the CH2 guys that the important part, the important part is that you're going to make something that looks like this CH2, OK? That has basically Iodines coming off of it, OK? So it's basically got a bond to here, a bond to here with like an Iodine coming off of it, OK I definitely drew that wrong but honestly the mechanism is not important that's why I don't even know the full mechanism it's just basically going to be a source of CH2, OK? I'm a little bit embarrassed that I didn't draw the full mechanism but to be honest it's because of we're using heavy metals with this Zinc and copper you're not going to be responsible for the full mechanism you just need to know the product, OK? So just imagine that you're basically making bonds to the CH2, OK? Now by the way one more word of advice this is not a carbene this is what we a carbenoid, OK? So that's why I said that you either need a carbene or a carbenoid, alright? So by the way if you're really interested in the mechanism it's on Wikipedia so that's your little research for the end of the day but I'm going to show you the product, the product has no iodines on it, it just has the CH2 so once again we're getting our cyclopropane and that's it and then the Iodines and the zinc just kind of they group together and they go out the solution, OK? So anyway guys so now you can see there's four different ways to add a triangle or a cyclopropane to a double bond, four different addition reactions but they all follow very similar mechanisms, alright? So hope that made sense, let's move on to the next topic.

You should not be responsible for the full mechanism of Simmons-Smith, but you should know what the reagents are, and be able to predict that it is a form of cyclopropanation. 

Carbenes and Cyclopropation Additional Practice Problems

Provide the reagent or starting material to perform the indicated transformation. More than one reaction may be required. You should number your steps if it is important for the synthetic transformation to take place.

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Supply the missing reagents for the following transformation. 

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Heating diazomethane generates nitrogen gas and a carbene. This question pertains to the structure and reactivity of the carbene species.

a) Draw a picture describing the geometry of the carbene that is generated, showing any orbitals that contain lone pairs or are empty.

 

b) On your picture from part a, indicate the types of orbitals that are present (s, p, sp 3, etc).

 

c) On your picture from part a, indicate in which orbital the lone pair resides.

 

d) On your picture from part a, identify any orbitals having nucleophilic character. Do the same for orbitals with electrophilic character.

 

 

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Propose a mechanism for the following reaction.

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Provide either the reagent(s) or the product(s) for the reaction below. This is not a mechanism question. Simply write the answer in the box.

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Consider the strucutres below and answer the following questions. 

f. Which disubstituted alkene forms enantiomeric pairs on treatment with CHCl / NaOH?

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Give the product, or products, including stereochemistry of the reaction of (Z)-3-methyl-2-pentene with the reagent below. If the products are a pair of enantiomers, you need to draw only one and state that the other enantiomer is formed. 

CHCl3, NaOH

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The creation of a cyclopropane ring from alkenes can be accomplished by two different methods. 

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The creation of a cyclopropane ring from alkenes can be accomplished by two different methods. 

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Synthesis: Provide the reagents for the following conversions.  Note that some transformations may require more than one chemical step. e.g. the acid step of a Grignard  reaction. For full credit, you must include and number these steps when necessary.

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Insert the missing curved-arrows for the following two reaction transformation.
Include all missing curved arrows.

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How many atoms and electrons are directly involved in the bond-making and bond-breaking of the reaction given below?  Choose the right answer. 

Addition of dichlorocarbene (CCl2) to propene

a) four atoms, two electrons

b) four atoms, three electrons

c) four atoms, four electrons

d) three atoms, two electrons

e) three atoms, three electrons

f) three atoms, four electrons

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Predict the product of the following reaction. Show stereochemistry when applicable. 

 

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Predict the products of the following reaction. Show stereochemistry when applicable. 

 

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Predict the principal organic product of each of the following reactions: 

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