Concept: Concept: Use of Protecting Groups5m
Now that we understand organometallics a little bit better, hopefully, you're aware of one of the major limitations that they have. And that limitation is that they tend to cross react with acidic hydrogens. So how do we prevent that from happening? Well, let's go ahead and talk about a strategy for that which is called protecting groups.
As I've explained before, organometallics are very powerful bases. They can obviously react as nucleophiles and attack electrophiles, but they can also react as bases and deprotonate things. What kind of things can they deprotonate? Well, they tend to just react with any acidic protons available and that ruins the reagent. What we've talked about already is that those acidic protons are usually stuff like carboxylic acid, very acidic; alcohol, pretty acidic; and water. These are all examples of protons that are so acidic that they're going to mess with the reagent instead of letting it react with an electrophile.
Let me give you an example. Let's say that I was trying to do a substitution reaction on this molecule. Notice that it has an alkyl halide on one side and an alcohol on the other. Now, notice that my reagent here is a Grignard. I've got my Grignard reagent. We know that the way that we like to draw Grignard reagents is as a CH3-. That tells my I've got a negative charge, it's going to attack some positive.
Alkyl halides, do CH3-'s or Grignards react with an alkyl halide? Absolutely. Remember that the alkyl halide happens to have a partial positive there. So I would expect to get an SN2 reaction on that alkyl halide.
But wait, we've got a problem. We've also got an alcohol on this molecule. That alcohol is going to be very acidic. What that means is that – notice I put pKa of 16. That's acidic enough to react with my Grignard. So what winds up happening is that instead of reacting in an SN2, that doesn't happen. It winds up reacting with the proton as an acid/base reaction. What we wind up getting is CH4 because now we've got the CH3 plus the H, and then you wind up getting a negative charge on the O. Now, by the way, the MgBr positive is just a spectator ion that happens to associate with the O.
This is considered ruined. This is not good. No bueno. Because now the Grignard can't react with the electrophile that I intended it to, which was this carbon right here.
So how do we prevent this from happening? Well, it turns out that alcohols can be protected. There are some strategies that we've used before to protect alcohols and this part is going to require a little bit of prior knowledge. If you've already learned about using protecting groups for alcohol, then we're going to review that right now. If you don't know how to use protecting groups for alcohol, then I would recommend going back to my lessons on protecting groups in the alcohol section and that will give you a better understanding, so you can understand this better.
But basically, there's two different ways, there's two different type of reagents that we can use to protect alcohols. Either we can use t-butyl ethers or silyl ethers. Both of them are two different ways to protect an alcohol from reaction. When you protect it, that means it's not going to be deprotonated by the organometallic. Instead, it's going to be locked up in that ether.
Just so you guys know, a really common acid that's used for protection is para-toluenesulfonic acid, which is kind of a long name, bit it's actually a very common acid in your book, but it's usually abbreviated. Instead of spelling it all like that, they usually say it that it's TsOH or that it's pTSA. Either way, both of them, just know that they're a source of H+ because this is an acid. An acid is used in protection. In a protection reaction, we always use one of these. We make an ether and the way we make it is through the reaction of an acid, like H+, and a double bond.
So for this problem, I'm going to go ahead and ask you guys to try to solve it on your own and try to get the final product. Now if you already have reviewed protecting groups from alcohol, then go ahead and try to solve it now. If not, if you have no clue what I'm talking about with protecting groups, then don't worry, just sit back and I'll explain the whole reaction in a second. So go ahead and try it out.
Concept: Example: Provide mechanism and final product of transformation.5m