Wittig Reaction - Online Tutor, Practice Problems & Exam Prep

The Wittig reaction is a crucial method for forming carbon-carbon bonds between aldehydes or ketones and ylides, resulting in regiospecific alkenes. The mechanism involves creating an ylide from an alkyl halide and triphenylphosphine, followed by nucleophilic addition to a carbonyl. This process generates a betaine intermediate, which transforms into an oxaphosphetane before yielding the desired alkene product. Notably, the reaction is regioselective but not stereospecific, allowing for the formation of both E and Z isomers when applicable.

Box-Out Method and Full-Mechanism

In this section, I'm going to teach you possibly the most important reaction of this entire chapter. Are you listening yet? Good, because you need to. This is called the Wittig or Wittig reaction and it's definitely going to be on your test. Let's get going. The Wittig, first of all, you pronounce it also Wittig because it's like German. I say Wittig but if someone says Wittig, don't freak out. This reaction is a special way to make new carbon-carbon bonds between aldehydes and ketones. What it's going to do is it's going to make regiospecific alkenes. What do I mean by regiospecific? Regio just talks about locations. It just means that I can make a custom alkene with whatever R groups on it I want. That's actually pretty helpful because most reactions that make alkenes have to do with elimination, and sometimes the R groups are kind of in different places. In this case, I can pick exactly where I want those R groups to be. In general, I'm going to show you an easy way to do things. I'm also going to show you the whole mechanism, of course. The easy way to think of it is that you have a reaction of a carbonyl and a molecule called an ylide. I'll define that more in a second, so an ylide. When a carbonyl and an ylide come together, obviously it's kind of a weird mechanism but the R groups wind up attaching to each other through an alkene and I get my regiospecific alkene as a product. If you were to get a question on your exam about a Wittig reaction and it's not asking for a mechanism, the answer to this question would be extremely easy because all you have to do is use the box out method. This is something that I this is like a Johnny special, clutch special. What's the box out method? The box out method says if a professor gives you a Ketone or Aldehyde plus an ylide, all you do is you take them and you face them towards each other so that the phosphorus from the ylide and the oxygen from the carbonyl are almost touching. Then what you do is you take your little combination there. You draw a box around the phosphorus and the oxygen. You start scratching out. You squint a little bit. Pretend like that's actually a big alkene in the back and that's your answer. Without a mechanism, without any crazy memorization, look at that. We get our answer which would be an H and an R in this case on one side that came from the carbonyl and then whatever R groups you had on your ylide. Really straightforward, it's one of the funnest reactions to use because it's an easy reaction to learn. However, we know that organic chemistry 2 professors are so mechanistic. They want you to know all the arrows. In case your professor is one of those, let's go through the entire mechanism. The first part is the formation of the ylide. It turns out that the ylide actually comes from an alkyl halide. That alkyl halide is going to react with a molecule called a triphenylphosphine. Tri phenylwhat? 3 benzenes phosphine. A triphenylphosphine has a very nucleophilic lone pair. That nucleophilic lone pair is actually going to be able to do an SN2 backside attack reaction. You would take your alkyl halide and you would use that as your leaving group and you would kick out the halogen. This is just an SN2 mechanism from your Orgo 1 glory days. What you wind up getting is now the X is gone. The phosphorus is there but now the phosphorus has a plus charge because it's not too happy with 4 bonds. It wants 3 bonds and a lone pair like nitrogen. Everyone cool so far? We don't have an ylide yet by the way. This is just the triphenylphosphine doing the SN 2 attack. Now keep in mind guys, everything you learned about SN 2 applies here. It's not going to work on what type of alkyl halide. Do you guys happen to remember this? Guys, if you're gonna learn anything in organic chemistry, know your backside attack. You can neve

Determine the carbonyl and ylide that formed the following product. 

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Here’s what students ask on this topic:

What is the Wittig reaction and why is it important in organic chemistry?

The Wittig reaction is a chemical reaction used to form carbon-carbon double bonds (alkenes) by reacting an aldehyde or ketone with a phosphonium ylide. This reaction is crucial in organic chemistry because it allows for the regiospecific formation of alkenes, meaning you can control the position of substituents on the double bond. This is particularly useful for synthesizing complex molecules with precise structural requirements. The reaction is named after Georg Wittig, who was awarded the Nobel Prize in Chemistry in 1979 for this discovery.

How is an ylide formed in the Wittig reaction?

An ylide is formed in the Wittig reaction by reacting an alkyl halide with triphenylphosphine. The triphenylphosphine performs an SN2 nucleophilic attack on the alkyl halide, displacing the halide ion and forming a phosphonium salt. This intermediate is then deprotonated by a strong base, commonly butyllithium (BuLi), to generate the ylide. The ylide has a positively charged phosphorus atom adjacent to a negatively charged carbon atom, which is crucial for the subsequent steps in the Wittig reaction.

What is the mechanism of the Wittig reaction?

The mechanism of the Wittig reaction involves several steps. First, an ylide is formed from an alkyl halide and triphenylphosphine. The ylide then reacts with a carbonyl compound (aldehyde or ketone) in a nucleophilic addition, forming a betaine intermediate. This intermediate rearranges to form an oxaphosphetane, a four-membered ring structure. Finally, the oxaphosphetane decomposes to yield the desired alkene and a byproduct, typically triphenylphosphine oxide. The overall process is regiospecific but not stereospecific, meaning it can produce both E and Z isomers of the alkene.

What are the limitations of the Wittig reaction?

While the Wittig reaction is highly useful, it has some limitations. One major limitation is its lack of stereospecificity, meaning it can produce both E and Z isomers of the alkene product. Additionally, the reaction is sensitive to the steric hindrance of the starting materials; it works best with primary and secondary alkyl halides and is less effective with tertiary alkyl halides. The reaction also requires the use of strong bases, which can limit its applicability with base-sensitive substrates. Despite these limitations, the Wittig reaction remains a powerful tool for synthesizing alkenes.

What is the difference between a betaine and an oxaphosphetane in the Wittig reaction?

In the Wittig reaction, a betaine is an intermediate formed after the nucleophilic addition of the ylide to the carbonyl compound. It features non-adjacent positive and negative charges. The betaine then rearranges to form an oxaphosphetane, a four-membered ring structure containing oxygen and phosphorus. The oxaphosphetane is a key intermediate that eventually decomposes to yield the final alkene product and triphenylphosphine oxide. Understanding these intermediates is crucial for grasping the full mechanism of the Wittig reaction.