The formation of five-membered ring ethers is an important goa...

Question

The formation of five-membered ring ethers is an important goal in synthetic organic chemistry because tetrahydrofurans are contained within a number of antitumor natural products. Toward that end, a one-pot synthesis of a bis-THF containing compound was developed (Eur. J. Org. Chem. 2010, 6263–6268). Suggest a mechanism for this transformation.

Chemical reaction diagram illustrating the oxymercuration of alkenes to form five-membered ring ethers.

Accepted Answer

Alright. Hi, everyone. So this question says that producing tetra hydro ferens is a major objective in synthetic organic chemistry because many anticancer natural products contain it provide a mechanism for this reaction. Now, in this case, our starting material is a dying. And in the first step, we have a reaction with mercury to acetate followed by sodium boro hydride. In the second step. Now recall first and foremost that based on this combination of regions, this is expected to be an oxy mercury deer curation reaction or oxy mercury reduction. Now, typically speaking in this first step involving mercury to acetate water would be added to ultimately produce an alcohol because water is not present in the actual synthesis. The two hydroxy groups present in the starting material are going to undergo an intra molecular oxy mercury reduction to create a tetra hydro Fyan on both sides. Recall that this process is Markov, Niko and anti addition. So with this in mind, let's go ahead and start with our mechanism and I went ahead and redrew the starting material towards the bottom of the screen. Now, the first step is going to involve a reaction between each respective pi bond and one molecule of mercury to acetate for each of them. So here, I'm just drawing out two molecules of mercury two acetate or too equivalent I should say. And the first thing that happens is that the pi electrons of each all keen are going to attack the electro mercury. However, recall that mercury does in fact have a long pair of electrons. So this is a concerted step where the pi electrons of the a keen establish a bond with mercury and mercury's loan pair of electrons establishes another bond between itself and carbon. This ultimately displaces one ion of acetate. Now recall it because this is a concerted step. Meaning everything is happening at the same time, this prevents the possibility of rearrangement. So at this point, the pie bonds have since broken and we have a cyclic intermediate in which mercury is connected to both carbons of the starting a key on both sides in this case. So here one ion of acetate has been produced as a result. And now generally speaking, if water had been added in solution, at this point, we would have seen a nucleic attack of water to the more substituted carbon of the mercurial ion intermediate. Note that mercury should have a positive charge. But in this case, water has not been added to the system, which means that the hydroxy groups present in the starting material are going to behave as the nucleo instead. So each hydroxy oxygen is going to attack the more substituted carbon of each mercu radium ion intermediate. This ultimately breaks the bond between carbon and mercury and creates a ring structure due to the fact that this is an intra molecular nucleic attack. So at this point, two tetra hydro fyan rings have been produced as a result. So we have one ring on one side and we have the other on the other side. Now keep in mind, however, that both oxygens from the hydroxy groups would each have a positive charge at this point due to the fact that they each have a proton attached to them. And so mercury is now attached only to the least substituted carbon of both starting all keys. So before we go on to the next step, let me go ahead and add the meth boxy groups that are also present. All right. So before we can go ahead and proceed with the step involving sodium boro hydride, the oxygen atoms from the starting hydroxy groups must be detonated. This is when we can recall that two ions of acetate formed during the first step of the mechanism. So here we have one ion of acetate that can deproteinate each respective oxygen atom from the hydroxy groups. This is ultimately going to make both oxygen atoms neutral. Now, the oxygen atoms are neutral to create the tetro Hydrophor rings. And now I'm going to go ahead and fill out the rest of the structure All right. So thus far, we have covered the oxy mercury phase or step of this particular mechanism. At this point, we introduce the deer curation or reduction step involving sodium boro hydride. So at this point, I'm going to take the intermediate and after the reaction involving sodium boro hydride, the bond between carbon and mercury is reduced, replacing mercury with hydrogen. So here we have a very similar end product except now, mercury is no longer present on carbon and there you have it. So here is the complete mechanism for this transformation. If you watch this video all the way through to the end. Thank you so very much and I hope you found this helpful.

Key Concepts

Five-Membered Ring Ethers

One-Pot Synthesis

Reaction Mechanisms

Watch next