The Day Has Finally Come!


Kelly, C.B.; Colthart, A. M.; Constant, B. D.; Corning, S. R.; Dubois, L. N. E.; Genovese, J. T.; Radziewicz, J. L.; Sletten, E. M.; Whitaker, K. R.; Tilley, L. J. Enabling the Synthesis of Perfluoroalkyl Bicyclobutanes via 1,3 γ-Silyl Elimination Org, Lett. ASAP March 2, 2011


So its out. On the ASAPs. AWESOME. After about 4-5 years of work and hours upon hours of writing and revising, our article is finally out in one of the most presigious organic chemistry journals out there (and my favorite in fact). Now time to give ya a brief summary of 4+ years of work in a few paragraphs. So the orginal goal of my project was to just explore gamma-silyl interactions in the cyclobutyl system. If you know the beta silyl effect, you kinda have a good idea of what the gamma effect does. The gamma-silyl effect, which really is just a form of long range neighboring group participation (NGP). Think of it like a acetate group performing anchimeric assistance. Below is the accepted mechanism for this sort of interaction, potentially yielding cyclopropanes upon elimination.



V.J. Shiner, Dr. Tilley‘s former PI, did a lot of work with this effect and found that he could affect gamma silyl elimination of gamma silyl cyclohexyl brosylates. He noted an interesting trend :i f the relationship was “W” or the gamma silyl group was in a cis relationship (B, green arrow) to the leaving group, he observed that cyclopropyl products formed in addition to rearrangement products and substitution. However if the relationship was trans, no cyclopropyl products were observed and only elimination and substitution without retention occurred (A, Red arrow). Shiner explained it as percaudal participation of the silyl back lobe with the forming cation (see below). However, cyclopropanation was only a minor product, giving at most 20% conversion to the small ring system.



I began work on this project in the summer of  ’07. My orginal goal was the preparation of bicyclobutane via 1,3 gamma silyl elimination  to form the brigehead bond. Now that’s truly a feat if you considered a cationic approach (which is much more difficult to control) has never been used to form just a bond in the cyclobutyl system and the amount of strain that would be introduced by forming such a bond. After getting to the desired gamma-silyl cyclobutanol, I attempted to put on leaving groups with mixed success. Any sort of reactive leaving group (i.e. tosylate, mesylate etc.) readily decomposed on workup. Other reactive groups like the iodide was stable but when solvolyzed gave only subsitution or rearrangment to give beta silyl elimination  It seemed that we wouldn’t be able to get our methodology to work in this sysyem. However, since we found that the tosylate was stable in solution, we attempted to pyrolysize it and collect the vapor coming off of the reaction. We were pleased to find that bicyclobutane did form, but only in 2.5% yield.



Going off of work by Gassman regarding NGP and electron-deficient cations (or destabilized cations if you will), I then investigated what would happen is we placed a electron-withdrawing group (EWG) at the cationic center. In theory, it should dramatically increase NGP causing the silicon to be much more electrophilic. The electrophilic Si should be readily eliminated at that point. So simply (if you can call two years of simply) modified my method to introduce a CF3 group and then tosylated it.  In December of 2009 I solvolyzed it to give a new bicyclobutane! Moreover as the only product of solvolysis showing the power of the EWG in enhancing gamma silyl participation. It took some time but in april of 2010 I finally isolated and purified the CF3-Bicyclo. When your compound boils at 28 oC, distillation becomes a real issue and forget columns or conventional techniques. However, I couldn’t get it more than 60% pure. Hence I turned my attention to writing up what I did while Professor Tilley focused on the purification. That summer after I graduated, Professor Tilley had his students synthesized the pentafluoroethyl derivative and, by using a 60/40 mixture of H2O to trifluoroethanol, he was able to successfully distill off the CF3 bicyclo in 97% purity. I’d say that was key to the success of our article. We also established a small collaberation with UC Berkely via a former Stonehill student, Ellen Sletten. One of the instruments at UC Berkley could do whats called a HOESY. We were able to determing the relative stereochemistry of the major isomer after trifluoromethylation. This gave us insight into the mechanism. It showed us that the cis isomer was indeed the one undergoing solvolysis, while the minor trans isomer failed to react. Annnnd thats enough for now. I hope you enjoy the article!!! Ckellz…signing off.

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