What I would call, kinda awesome…

Yejian Han, Lizhi Zhu, Yuan Gao, and Chi-Sing Lee A Highly Convergent Cascade Cyclization to cis-Hydrindanes with All-Carbon Quaternary Centers and Its Application in the Synthesis of the Aglycon of Dendronobiloside A Org. Lett. ASAP Publication Date (Web): January 10, 2011

Oh Boy…My first review. I’ve waited my entire life for this. I would like to thank all th.. Wait what am I saying. I’m only doing this because I’m in between matches in SC2 (and for n00bs, thats’ Starcrack Starcraft 2) PLUS I’m snowed in…literally. Not that I would go outside anyway but I hate a restriction of autonomy…anyway on with the chlorophyll…I mean review.

I decided to review a article straight outta the People’ Republic. Chinese chemistry has really come a long way and I’d say a third of what I see in journals like Org Lett. or JOC comes from our Asian friends. First off, the Lee group has done some pretty good work here. They are doing what I would call straight CHEMISTRY. My favorite. No real bio stuff, but it does have bio applications (and I could tell they were stretching on that because the “natural products” that they said contained these motifs…one was a Chinese herb that showed minimal promotion of the immune system in vitro and another was a presynaptic inhibitor of the spinal chord…of frogs). Despite the limited applications, it’s a good methodology. These guys really did their homework. They give a good history of carbocyclic rearrangements of unactivated alkynes and silyl-enol ethers. I didn’t know it wasn’t really known until the mid-80s and Cornia discovered it using HgCl2 (wouldn’t of wanted to be in that lab…). More over its been pretty popular. Trost did some work with it in 2006 and 2007 using a palladium and gold catalysts respectively. He  went as far as to make it asymmetric (a word I tend to hate, but I recognize the importance).

Lee, however, wanted to do more. The premise was pretty simple; he wanted a catalyst that would not only cyclize but also promote a Diels-Alder (DA) to get a double ring annulation. It would go something like this: do a Diels-Alder reaction similar to Danishefsky’s diene with the TIPS silyl-enol ether to give the first annulation to get the six-membered ring. . The new silyl-enol ether  (double bond now between R1 and the -OTIPS carbons) is in the perfect place to undergo a carbocyclic rearrangement with the now-electron-deficient alkyne (thank to coordination of the alkyne to the Lewis acid). As for how they went about it…they screened a number of lewis acids from AgOTF to ZnI2 and solvents from DCE to Toluene using a previously know silyl-enol ether and acrolein (R2,R3 = H). There was a logical progression. They got their first hits with zinc species and then just varied the anion and solvent until they were happy. Reaction time seemed to play a minimal role. And DR was pretty good (12:1 endo (EWG trans to H, R1 in product)/exo (EWG cis to H, R1 in product) under their optimized conditions). They then did what every good methodology paper does: explore the scope! The scope was somewhat disappointing due to its limited nature. However, they were able to vary the structure of the silyl-enol ether slightly and use other dienophiles. But I’m betting they tried more and they lost either yield or the DR just based on the limited nature of the scope. I think this kinda reaction is somewhat substrate specific. Either that, or they thought they had competition and published as fast as they could because synthesizing a library of those ethers is somewhat steppy (4 steps to just get a starting material…).    Regardless, it still is a nifty reaction cause it creates a quad center and two rings at the same time.

They then did a mini-total synthesis of a aglycon of that Chinese herb compound I mentioned earlier. Interestingly they starting from the cyclized product obtained from  the reaction  used to optimized their conditions (which makes me suspicious of the scope work but hey, its peer reviewed…*looks other way*). If you count that step required to syntheize the silyl-enol ether, we are looking at a 11 step synthesize with an overall yield of *breaks out calculator*…14.2%. As far as total syntheses go thats’ actually pretty respectable, so props to you Lee and coworkers. They end with a classic line ‘we are investigating the use of this reaction to make bicyclic systems and for natural product syntheses”. Well done, certainly one of the better articles I’ve seen from the People’s Republic. Ckellz…signing off…

***Just as a note, I noticed a error in my structure of the agylcon of dendrobiloside A, there should be a hydroxyl group off of that bolded methyl group…sorry!


1 Comment

  1. […] I can say is this is probably one of the best articles I’ve read in some time. It puts the last paper I reviewed to shame. Really to shame. I mean this article is on a COMPLETELY different topic, but […]

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