I Have Returned!!

Li, H; Li, W.; Liu, W.; He, Z.; Li, Z. An Efficient and General Iron-Catalyzed C-C Bond Activation with 1,3-Dicarbonyl Units as a Leaving Groups Ang. Chem. Int. Ed. Vol 50 pg 2975-2978, March 21st, 2011

 Wow. Seems like the last time I posted was in the Stone Age. But I’m back after way too long. I’ve been unbelievably busy lately between teaching, classes, and research. But a lot of exciting things going on in the lab. Our collaboration with Professor Tilley is going quite well. We are close to knocking off two substrates and we have an addition few more to make. I also managed to come up with a brand new methodology!!! I’m really excited about that one. I can’t reveal the details (yet!) but this one is pretty big. And I also have a lot of new toys coming in to help me out with some of the synthetic work that I’ve been doing. I’m gonna be getting a brand spanking new manifold which I am extremely excited about and some more equipment to use in and around the lab. But I haven’t forgot to keep up with the literature. I’ve been keeping a list of articles that I definitely wanted to review and this one is one of them.

Just like benzyne and the trifluoromethyl group, I love carbocation-based methodologies. I love them partially because of my gamma-silyl routes but also because cations are remarkably difficult to control. So, if a group is able to successfully utilize carbocations to affect a particular transformation, I think that shows the capabilities of the group. It may not be the most AMAZING chemistry, but it is certainly commendable. And that’s why I really loved this article. Not only did they control cations, but they essentially developed a new leaving group (one that I wouldn’t have thought to try). (Fan Boy alert!!!) That’s kind of why I really loved Lambert’s use of cyclopentadiene as a leaving group

So the article starts out by listing some of the common leaving groups (Sulfonic esters, halogens, etc.) and traditional substitution reactions rely on C-X bond dissociation in order for the incoming nucleophile, Y, to form a C-Y bond. They also mention that in recent years researchers have been looking into alternatives to leaving groups and have been looking at compounds with high strain or that are semi-stable carbanions (such as the oldest of these, CN-). Now here’s where they got me hooked. They weren’t looking for this reaction, they discovered it by accident doing other work. And they came right out and said that. But being remarkable efficient scientists, Li’s group pursued the chemistry. When working with structures of type 1 they found that in the presence of FeCl3 (catalytic amounts too!) and 2, they obtained both 3 and 4.

The only explanation they could come up with led them to an unprecedented reaction: The 1,3 diketone was acting as a leaving group and proceeded through C-C heterolytic bond cleavage. They immediately turned their attention to screening general reaction conditions, ultimately finding that 1 was in fact the best diketone for this sort of cleavage. They attributed this to the high stability of the forming anion (don’t worry a mechanism will come!).


After determining which diketone was the best substrate, they performed a little Friedel-Crafts chemistry. A variety of aryl compounds underwent electrophilic aromatic substitution (EAS) reactions with diphenyl cation including indoles, phenols, furans, and thiophanes. Not really any unusual occurrences there. We all know cations react with aromatics and indeed their compounds were the thermodynamic products expected from EAS chemistry.

They then began changing their cationic piece. Using 5 a model aromatic, they were able to substitute a variety of diaryl, monoaryl, and allylic compounds (again all chosen because of cationic stability and limited rearrangement). Interestingly, when comparing their cation to cations normally formed via removal of benzylic hydroxyl groups by iron (III) chloride, they found that their methodology was less prone to alkylation of heteroatoms (i.e. alkylation the indole nitrogen rather than EAS)

They next tried alkenes and alkynes. Note surprisingly these compounds underwent electrophilic substitution followed by a EAS step for form very nice indane (alkene) and indene (alkyne) products. If performed at room temperature, they obtained the acyclic alkene products, whereas heating preferred the indane/ene products.

Here’s were I had a huge question. They noted that trans-stibene and cis stibene had a disparity in reactivity. That, to me, is unusual because I would expect that since there these two are iso-electronic, there would be no difference between the two. Hence, its possible that their iron may have trace amounts of palladium in their FeCl3 (or some other transition metal) and some sort of organometallic reaction is actually taking place. I have a hard time accepting my own argument just based on the plethora of examples they have which, if this as all C-H bond activation, would be remarkable coincidental and highly unusual. Therefore, despite some concerns, I still think that their proposed mechanism is correct:

Overall, this was an excellent article by Li and co-workers so hats off! Even though the conditions are somewhat harsh, as a novel methodology this is certainly at par. I hope to be posting more soon so stay tuned! Ckellz…Signing off…


1 Comment

  1. According to their mechanism, it looks like this reaction won’t work if the diketone is trans-fixed, like indandione or somesuch. Too bad for me – I’m having a problem with a trans-fixed 1,3-diketone, which doesn’t want to participate in Knoevenagel reaction. Well, to be more exact, it does react – but the product reacts further with another molecule of the diketone in a Michael reaction as soon as it is formed. This article initially looked like a chance for a way out of my rather unpleasant situation…

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