An eyesore here, a gem there

If I told you that there are some real eyesores in synthesis, I am sure you will know exactly what I mean. We have all been there. For example, you run a cyclization reaction and note that the best yields you record are for the so-called gem-dimethyl containing substrates. The reason is that you need some help from the Thorpe-Ingold effect that contributes to improved kinetics of cyclization by reducing the number of accessible conformers (plus some other reasons). Or you need a pro-nucleophile with a pKa that is suitable for the weak base you intend to use. Then you use a gem-diester. Again, you are stuck with it at the end, although this case is not as bad as the gem-dimethyl example. At least you have decarboxylation chemistry in your disposal and can “erase” one of the ester groups (if the rest of your molecule tolerates your conditions of choice, of course). At some point you feel dejected as no one asks questions along the lines of “Have you tried your reaction without the two methyl groups?” because everyone knows that you need the Thorpe-Ingold effect. They just give you a look that says “poor you”… It seems that gem-“anything” is bad news.

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But not necessarily. For a number of reasons, my lab has been looking at gem-dichloro aldehydes. Is this another one of those “gems”? I recalled to mind a great paper published by Tom Rovis and colleagues several years ago. In it, Tom showed a useful application for a molecule that contains a pair of “gem-offending” chlorines. In this case, what happens is a carbene-mediated transformation that leads to amide bond formation. Very cool stuff.

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http://pubs.acs.org/doi/abs/10.1021/ja0764052

2 thoughts on “An eyesore here, a gem there

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