Acetals as Protecting Groups

Concept: Concept: Protecting Groups

3m
Video Transcript

Now let's talk about a synthetic application of acetals and that's to use acetals as protecting groups. Let's look at these two molecules above me. What we’ll find is that these molecules are in equilibrium. We have learned word that if you expose a carbonyl to alcohol and acid, you can basically make an acetal. In this case since this is a cyclic acetal, I would expect to be using a cyclic diol in combination with acid. I’ll just put H+ to give me my cyclic acetal.
What's important about the difference between these is that there's a huge difference in reactivity between my original carbonyl and my acetal. Notice that my carbonyl has an extremely reactive partial positive pi bond. Whereas an acetal does have dipole so it does have dipole similar to the carbonyl. But notice that they're located on sigma bonds not on a pi bond. All of these bonds are extremely difficult to break. In fact, an acetal is about as reactive as an ether. Just remember how reactive ethers were. Pretty much unreactive. Ethers barely do anything. All that you can do is combust them. Sure, they blow up. But then others in combustion they don't react and that’s because these single bonds are extremely difficult to break.
If I ask you which one is the safer version, if I was to run a reaction somewhere else on the molecule, which one is safer to have around, a carbonyl or an acetal? The answer is an acetal because an acetal really isn't going to react with almost anything. Whereas a carbonyl is so reactive, we’ve learned they can even react with water, so we want to protect it. That's the whole idea behind a protecting group. Acetals are used to protect sensitive aldehydes and ketones from reaction with other reagents since they’re reversible. The idea being that you can turn the carbonyl in to an acetal, do your reaction somewhere else and when you're done, you can go ahead and hydrolyze it back to the original carbonyl, sparing it from reaction with your second reagent.
I want you to look at this example. I want you guys to devise a synthesis for this. I want you to look at these two molecules and figure out what would be the best way to make that first molecule into the second one. I’m going to give you a hint. This is not a one-step reaction. If you try to do it in one step, you’re going to fail. Try to think about what reactions you could and what sequence to make this transformation happen and then I'll show you.