Stille Reaction: Videos & Practice Problems

The Steely reaction is a cross-coupling process where an organostannane reacts with a carbon halide to form new carbon-carbon bonds, producing conjugated compounds like alkenes and styrenes. The mechanism involves three key steps: oxidative addition, transmetalation, and reductive elimination, facilitated by a palladium catalyst. This reaction is stereospecific, maintaining the E/Z configuration of vinyl groups, which is crucial for determining the product's structure. The overall goal is to create more stable conjugated products while regenerating the palladium catalyst for further reactions.

Stille Reaction

In this video, we're going to take a look at the Stille reaction. Now, in the Stille reaction, an organostannane compound reacts with the carbon halide in order to form a new carbon-carbon bond. We're going to say the reaction creates conjugated compounds composed of alkenes, styrenes or biaryl compounds. If we look at the general format for a cross-coupling reaction, we know that it's composed of a carbon halide in the form of usually R₁X, reacting with a coupling agent in the form of R₂C. And here we use a transition metal complex, in order to create a coupling product and then we'd have byproduct waste. Now, if we compare this to the Stille reaction, we still have a carbon halide being used. Then our coupling agent is our organostannane compound. And remember, stannane is just another term we can use for tin. So it's really just an organic tin compound. Here we use a palladium catalyst, and that's going to help us create our coupling product. And then we have here. So in terms of R₁, R₁ of the carbon halide is represented by a vinyl, aryl, or allyl group. R₂ can be represented by a vinyl, aryl, and also an allyl group. When it comes to C, for our Stille reaction, it's in the form of Sn connected to 3 R groups. These 3 R groups are in the form of alkyl groups such as methyls or ethyls or butyls. And X, like we're used to seeing when it comes to the carbon halide, it just represents a good leaving group in the form of chlorine, bromine, iodine or a triflate.

Now, here we have the general layout for the Stille reaction. So what's really going on if we look at it in terms of simplicity? We're saying here that we have the X group of our carbon halide and then the tin portion of our organic tin compound, they're being lost together, and what's happening is that R₁ and R₂ are bonding together. So that's the basic premise of the Stille reaction and that's what we're going to take and use to get answers for Stille reaction questions. Now, when we get to the mechanism itself, we'll see how exactly do we create the product. But for now, guys, click on to the next video and just take a look at the practice question. See if you can identify what the answers will be at the end. And one huge thing in terms of these types of reactions is that when creating conjugated dienes, the reactions observed to be stereospecific with retention of configurations. So what does that mean? That means that if your R₁ or R₂ is a vinyl group, then it maintains its E or Z configuration, if it has one. So keep that in mind. If R₁ or R₂ are of a vinyl group, then you have to pay attention to the stereochemistry at the alkene site. So is it an E configuration or is it a Z configuration? This will dictate what kind of product you're going to make. Now that we've gone over the basic layout of a Stille reaction, attempt to do the practice question, come back and see does your answer match up with mine.

Determine the product from the following Stille Reaction.

So here it states to determine the product from the following Stille reaction. Here we have our carbon halide, meaning that this portion represents our R1 group. We also have our organotin compound, indicating that this portion is our R2 group. Remember, fundamentally what's happening is we're losing the X group, or halogen, from our carbon halide, and the SnR3 group. As a result, R1 and R2 are going to combine together. Both R1 and R2 are vanillic groups. As a result, we must pay very close attention to the type of E or Z configurations they possess. Both of them have E configurations, so our products must maintain these E configurations. So we're going to write out R1 first, with our benzene ring. Since it's E, we must ensure it stays E. Now, we're going to draw in the R that's connecting to it, the R2 that's connecting. This alkene portion here is still E, and this alkene portion is still E. We are able to maintain the configurations of both the vanillic portions of R1 and R2 while giving us a product that is more conjugated. This would be our final answer for this question. Now that we've handled this simple practice question, click on to the next video and see how exactly the coupling mechanism works for Stille reaction.

Stille Reaction

So the Stille reaction contains the 3 major steps that we'll grow accustomed to seeing with a typical coupling reaction. We have step 1 with oxidative addition, step 2, transmetalation, followed by step 3 with reductive elimination. With oxidative addition, it involves the addition of the carbon halide to the transition metal complex. Here we have the lone pair on the palladium, which comes from its d orbital electrons. We know that this will attach to our X group of the carbon halide, while at the same time this bond here breaks and connects to the palladium. We know that our new complex has the palladium still with its original ligands, but now having attached to it our R1 group and our X group. From there we move on to step 2 which is transmetalation, where the R2 group transfers from the organotin compound to the palladium metal complex. What's going to happen here now is this bond's going to break, attach here to the palladium, cause this halogen to leave and attach to the tin structure. We're going to get our palladium having still its 2 original ligands, but now being connected to R1 and to R2. And then as a byproduct, we have our tin structure with the halogen attached. Finally, for step 3, we have our reductive elimination step where our coupling product is formed and we have the regeneration of our palladium catalyst. We will bring this down (my R1 group) to attach to my R2 group. This bond will break and the electrons will go back to palladium. What we wind up making is our coupling product, which is R1 attached to R2, plus the regeneration of our palladium catalyst. This is going to be a common theme that we're seeing with coupling reactions. We are trying to make a product that is more conjugated, therefore more stable, and that's one driving force. At the same time, the reaction is occurring because our transition metal catalyst is trying to reach an 18 or electron count to be more stable. At the end, we have the regeneration of our palladium catalyst, so it no longer has an 18 or 16 electron count. Therefore, it wants to undergo this process yet again in order to get closer to the 18 or 16 electron count. By going through the process again, we can therefore make even more of these stable conjugated products. Just remember when it comes to this or carbon halide and we're trying to lose the SN3 group for our organotin compound. As a result of this, we're going to connect R1 to R2 to make our more conjugated product.

Determine the product from the following Stille Reaction.

So, here it says determine the product from the following Stille reaction. Alright. So, we have tin here as part of this compound so this must represent our organotin compound. So we know that the tin component represents C so the alkene portion would have to represent R2. Over here next to it we have our halogen connected to benzene, so this must represent our carbon halide. So that would mean that this structure here represents R1. We know that for R1 and R2 combined together we have to incorporate palladium connected to 2 acetate ions. Alright. So we know that the general setup of this reaction is we have the tin component and the halogen are basically lost in the process. We've seen the mechanism for this reaction so we know that those two pieces are lost so that R1 and R2 can combine together. At the end, remember, because our R2 group is an alkene component or vinyl component, we know that all that's going to happen is that the tin portion gets replaced by all of this here for R, R1. Alright. So, where the tin component was we're going to put the R1 component there. So we have the benzene part, still with the SL3H group attached. So, here this will represent our final product. The alkene component for R2, it doesn't have any E or Z configuration so we don't really have to worry about that. So technically for this question, I could have placed the R1 group here pointing down or I could have placed it here pointing up. It really wouldn't matter because again the alkene component of R2 is not E or Z in terms of configuration. Now that we've seen this example or this practice question, move on to the next one. We have to determine what the final product will be for this particular Stille reaction. So, attempt it on your own. Come back and see if your answer matches up with mine.

Determine the product from the following Stille Reaction.

So here we're supposed to determine what the product will be from the following Stela reaction. If we take a look at the compounds that are reacting, we have triflate that's in place on this compound here. Remember triflate acts as a good leaving group like the halogens of chlorine, bromine, and iodine. So that would mean that this portion here represents our R1 group. It is part of our carbon halide in this case where we don't really have a halogen; we have a triflate instead. Then, if we look at the other compound, here's our tin component connected to three butyls, so this must be my organostannane compound. So that would mean that this portion here is represented by R2. In this particular case, R2 is an allylic component. Usually, we don't see allylic components. We see mainly vinyl and aryl components. But here for this reaction, it is possible to use an allylic group. Now, we know that all that's going to happen is that we're going to have the loss of OTF (triflate) with the tin component here. And we know that R1 and R2 are going to combine together due to the use of a transition metal catalyst. Here our transition metal catalyst is palladium connected to four PPH3s. So, at the end, what we're going to get is our R1 group connected to our R2 group. So here's our allylic position which is here and it's connected still to these two double-bonded carbons. So that would be our final product in terms of this Stela reaction. Remember, when it comes to these coupling reactions, rely on the general or generic layout of a cross-coupling reaction, find what R1 is, find out what R2 is, make sure that they're connected together by the aid of some type of transition metal catalyst and you'll be able to find your final answer.

Here’s what students ask on this topic:

What is the Stille reaction in organic chemistry?

The Stille reaction is a cross-coupling process in organic chemistry where an organostannane (an organic tin compound) reacts with a carbon halide to form new carbon-carbon bonds. This reaction is facilitated by a palladium catalyst and is used to produce conjugated compounds such as alkenes, styrenes, and biaryl compounds. The mechanism involves three key steps: oxidative addition, transmetalation, and reductive elimination. The reaction is stereospecific, maintaining the E/Z configuration of vinyl groups, which is crucial for determining the product's structure.

What are the steps involved in the Stille reaction mechanism?

The Stille reaction mechanism involves three major steps:

1. Oxidative Addition: The carbon halide adds to the palladium catalyst, forming a complex with the R₁ group and the halide.
2. Transmetalation: The R₂ group from the organostannane transfers to the palladium complex, replacing the halide.
3. Reductive Elimination: The R₁ and R₂ groups couple to form the final product, and the palladium catalyst is regenerated.

This sequence ensures the formation of a stable, conjugated product while allowing the palladium catalyst to be reused.

What role does the palladium catalyst play in the Stille reaction?

The palladium catalyst plays a crucial role in the Stille reaction by facilitating the three key steps: oxidative addition, transmetalation, and reductive elimination. During oxidative addition, the palladium catalyst forms a complex with the carbon halide. In the transmetalation step, it helps transfer the R₂ group from the organostannane to the complex. Finally, in the reductive elimination step, the palladium catalyst enables the coupling of the R₁ and R₂ groups to form the final product. The catalyst is then regenerated, allowing it to participate in further reactions.

Why is the Stille reaction considered stereospecific?

The Stille reaction is considered stereospecific because it maintains the E/Z configuration of vinyl groups throughout the reaction. This means that if the starting materials have a specific stereochemistry, the final product will retain that configuration. This stereospecificity is crucial for determining the structure and properties of the resulting conjugated compounds, making the Stille reaction highly valuable in synthesizing complex organic molecules with precise stereochemical requirements.

What types of compounds can be synthesized using the Stille reaction?

The Stille reaction is versatile and can be used to synthesize a variety of conjugated compounds. These include alkenes, styrenes, and biaryl compounds. The reaction is particularly useful for creating complex organic molecules with specific stereochemical configurations, making it valuable in the synthesis of pharmaceuticals, natural products, and advanced materials. The ability to form stable carbon-carbon bonds with high stereospecificity is one of the key advantages of the Stille reaction.