Friday, July 10, 2009

Enantioselective Total Synthesis of the Potent Anti-inflammatory (+)-Myrrhanol A
Victoriano Domingo, Lucia Silva, Horacio R. Dieguez, Jesus F. Arteagas, Jose F. Quilez del Moral, and Alejandro F. Barreo
Link to the Paper

So this latest taste of Science is freshly out of Spain. The main reaction here which caught my eye was the Ti catalyzed radical cyclization, forming a few new bonds and creating 3 stereocenters. Some other good science: a nice Negishi Carbometalation, a Suzuki using 9-BBN, and a nice epoxidation followed by reduction.

Well they started early with the Ti cyclization. It has a radical mechanism where the Titanium catalyzes a heterolitic bond breakage between the oxygen in the epoxide and the more highly substituted carbon in which its attached to. They formed this epoxide using DMAP. This carbon then attacks the neighboring sp2 carbon to form a chair, generating the sterocenter. This then pushes one electron from the pi bond over to then react with the other alkene in the same chair which then eliminates giving the lone electron back to the Titanium. Quite the proposed mechanism, but I love the end product of this reaction. It reminds me of the excitement I once had from studying the Diels Alder and the two bonds and stereocenters it formed. Here's the paper they referenced on this step PDF.

The next reaction in their synthesis was their chiral epoxidation. It looks as though the Chirality was obtained via the steric bulk of the adjacent methyl and other parts of the ring structure. After this they simply used LiAlH4 to reduce the epoxide on the less substuted carbon, affording the alcohol on the tertiary carbon.

Here is a reaction I had to do some reading on to understand. The Negishi Carbometalation has a very interesting mechanism. Essentially the Zirconium acts as a total theif and steals the Aluminum's methyl along with its electrons from the bond then stabilizes it with its two chlorine. It then sits down onto the alkyne similar to how you see HCl act with the negative chlorine, or in this case methyl, going to the more substituted carbon. After this the Zirconium and the Aluminum switch bonds the methyl on the Aluminum and the bond from the alkene on the Zirconium. Finnaly they add I2 to t solution, one iodine bonding to the Aluminum and one to the alkene. This explanation is pretty rough around the edges so if you want to check out the paper yourself here it is.

One of the later reactions of this paper was the Suzuki using 9-BBN. Here the 9-BBN was used to reduce the alkyne and place a steric Boron group on the terminal carbon. This step was followed with a Pd coupling with the vinyl idoide. I like the versatility of this step and its getting me to think about different ways to incorporate Boron groups into various structures.

Lots of fun Organometalics in this one.

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