Amazingly, just substituting different alkanes on the silicon makes a big difference in how easy the group is to remove. TBS is removed most readily by F-. With TBS in our toolkit, we are now ready to solve the retrosynthesis problem at top: The TBAF is a source of fluoride; its structure is this: Alkynes in synthesis Alkynes can be used together with Grignard reagents: Another option is the bulky base lithium diisopropylamide LDA.
So we'll start with a very simple molecule like that. And we'll go ahead and already make our Grignard reagent. And we're going to make methyl magnesium bromide, so methyl magnesium bromide we're going to add in our first step. We're going to use her as our solvent. And in our second step, we're going to add H3O plus. Now, when you're analyzing a Grignard reagent, you pretty much have to think, where's my carbanion?
So this carbon right here is negatively charged. That's the carbon that's going to attack my carbonyl. So if this carbon attacks my carbonyl, right?
And the electrons kick off onto here, right? As our intermediate, we would have hydrogens on either side of our carbon. A negatively charged oxygen up here. And the R group, this time, is a methyl group like that. So after you protonate it, right, in the second step. So after these, so we'll just say, these lone pair of electrons are going to pick up a proton from H3O plus, right?
We would form this carbon with two hydrogens. We're going to protonate our alc oxide to form an alcohol up here for our product.
And if you look at that molecule closely, you'll notice it is ethanol. So you make a primary alcohols if you use formaldihide. So this is a primary alcohol. Its primary because the carbon attached to the OH is attached to one other carbon. Let's see how we can make secondary alcohols. OK, so this time you need to start with an aldehide. So instead of two hydrogens on either side of your carbon, as we did before, this time you have to have an R group on one side.
So this will be our aldehide, like that. All right, and let's go ahead and use the same Grignard reagent. We use methyl magnesium bromide again. Like that, and second step, H3O plus.
So once again, think about what is your nucleophile. So the negatively charged carbon is going to be my nucleophile. Is going to attack my carbonyl, kick these electrons off. So once again, when we draw the intermediate, all right, up at the top here.
We have our alc oxide anion, negatively charged. The hydrogen is still there. And what we did was, we added a methyl group on. So this CH3 at the bottom of our intermediate came from our Grignard reagent.
And once again, acid based chemistry, to protonate the alc oxide, we'll form our secondary alcohol like that. So that would be the secondary alcohol that is produced from this reaction. Once again, this carbon is attached to two other carbons, making this a secondary alcohol.
All right, so one more example here. This time we will react our Grignard reagent with a ketone. So we'll start with our ketone over here, on the left. So here's our ketone. So it's cyclohexanone. And once again, let's stick with methyl magnesium bromide. And so we have methyl magnesium bromide that we add. And again, our solvent is ether, excluding water. And second step, we're going to add a source of proton. So once again, the exact same mechanism, exact same thinking involved.
The reduction of cyclohexanone by hydrogen gas with a platinum catalyst produces cyclohexanol in good yield. The reduction of a carboxylic acid: leads to the formation of a primary alcohol: This reduction requires a very strong reducing agent, and lithium aluminum hydride is the standard choice. What bonds would form and break? Likewise, working backwards in the context of chemical reactions is a new thing for many people. It takes practice to apply! Breaking bond A retrosynthetically gives us butanal and methyl Grignard.
Breaking bond B retrosynthetically gives us ethanal and propyl Grignard. After each Grignard reaction we need to do a mildly acidic workup so that we end up with the neutral alcohol.It all depends on what sort of carbonyl compound that you're starting with. We use methyl magnesium bromide again. So we now have, we now have our R group directly attached to our, what used to be our carbonyl carbon. What bonds would form and break? So we have a magnesium with two positive charges. Reactions of alcohols Video transcript In this video we'll see how to synthesize alcohols using the Grignard reagents.
And then my carbonyl, right?
So these two electrons right here are going to come off, onto the halogen. As shown in the following figure, a hydrogen ion catalyzes the Markovnikov's addition. Because organometallic reagents react as their corresponding carbanion, they are excellent nucleophiles. So you make a primary alcohols if you use formaldihide.
So this is our carbanion. Its primary because the carbon attached to the OH is attached to one other carbon. I'm going to draw magnesium's two valence electrons like that. So carbon is bonded to magnesium.
Now, in terms of electronegativities, carbon is actually more electronegative than magnesium. So let's now take the Grignard reagent we just formed, and let's make an alcohol with it. Again, I mixed up the halides with the Grignards here, just for variety.
All right. Likewise, working backwards in the context of chemical reactions is a new thing for many people. OK, and let's show the different types of alcohols that can be produced. So a lone pair of electrons on our oxygen takes a proton from H3O plus, leaving these electrons behind to form water. All right, so this is our generic reaction. In the next video, we'll take a look at more about Grignard reagents, and we'll talk a little bit about how to work backwards and think about synthesis problems.
Right, so we now protonate our alc oxide to form our alcohol, like that. Following are two examples of complex metal reductions: Lithium aluminum hydride is a very strong reducing agent that will reduce many functional groups in addition to aldehydes and ketones. The simplest way to achieve this is with as trimethylsilyl TMS; Me3Si : In other words, TMS will form an ether with your alcohol, and can be removed again upon addition of acid or base. Recall that Grignards add twice to esters. The reduction of cyclohexanone by hydrogen gas with a platinum catalyst produces cyclohexanol in good yield.
One valence electron. Magnesium has donated both of its electrons. And it's radical because that electron is unpaired.
Like that, and second step, H3O plus. And the magnesium that we started with donated an electron. Ryan Spoering on April 6, And that's going to form our product.
Right, so this top oxygen here now has three lone pairs of electrons, negatively charged. And this time I'll draw in all of my lone pairs on my halogen, like that. One valence electron. And let's go ahead and draw what would result. We're going to use her as our solvent. And this carbon here came from our carbonyl, and this R group is going to attach to that carbonyl carbon.
We now have this carbon with one electron around it on the right side, like that. This fact provides us with a useful method for ascending a homologous series. So H3O plus. For example: One important route for producing an alcohol from a Grignard reagent has been omitted from the discussion in the reading. And so we have methyl magnesium bromide that we add. Magnesium has donated both of its electrons.
Sodium borohydride is a much weaker reducing agent that basically will reduce only aldehydes and ketones to alcohols. So it's a very useful reaction because it's a carbon, carbon, bond forming reaction. So a lone pair of electrons on our oxygen takes a proton from H3O plus, leaving these electrons behind to form water. Ryan Spoering on April 6,
I've drawn it like a covalent bond. And then this carbon right here.