Without a Trace

No, not the TV show or the Giuliani campaign as David Letterman quipped earlier this year, but rather the use of traceless tags in parallel synthesis. With any strategy that employs tags, be they solid phase, ionic, or fluorous, at the end of the synthesis you have to remove those tags. So if it takes four steps to assemble your desired molecule, you then need a fifth step to remove the tag. Usually that’s not a big deal, but it does add a step to the overall reaction scheme. Traceless tags are those that are incorporated into the synthesis so that the last step is also a detagging step. A good example of this is the samarium chemistry of Prof. David Procter’s which was summarized a couple of posts ago.

Just available online as a J. Org. Chem. article is another example from the UK. This time from Prof. Adam Nelson and co-workers at the University of Leeds. (Sidebar: This article is free to anyone, including non-subscribers thanks to Prof. Nelson who used the ACS Author’s Choice program, which makes articles freely accessible if the author pays a fee. And it’s not a nominal fee, either.) In their report, they construct heterocyclic rings from open fluorous-tagged oligo-olefins through tandem ring closing metathesis. The nifty part is that the last olefin metathesis in the cascade achieves three things; a) it completes the synthesis of the heterocycle, b) removes the fluorous tag from the heterocycle, and c) releases the metathesis catalyst back to the reaction mixture. The reaction mixture was then purified by F-SPE which easily separated the desired compound from fluorous tagged reaction by-products.

So that’s all fine and dandy, but why have the fluorous tag there to begin with you might ask? That’s where the real value of the fluorous approach kicks in. The synthesis of the olefin metathesis substrates was conducted using a number of Mitsunobu reactions employing 4 equiv. each of DIAD, triphenylphosphine, and the non-tagged alcohol. In other words, a purification nightmare if you were not using a fluorous tag. Each of these reactions, however, was easily purified using F-SPE. With the methodology worked out, including facile, and general, purification steps, the authors plan on moving forward to the synthesis of more complex molecules in diversity-oriented syntheses.

This entry was posted in FSPE, Library Synthesis and tagged , . Bookmark the permalink.

Comments are closed.