Posts Tagged ‘Julius Rebek’
Danishefsky + Rebek = ?
by Phil on Jun 18 2008 (4012 Views)I recently wrote about the reaction of isonitriles with carboxylic acids under microwave irradiation, as reported by Danishefsky. Rebek’s group took up this idea and tried the reaction inside capsules formed by two cavitands (DOI:10.1021/ja802288k).
In the presence of the capsule, acid 1 and isonitrile 2 react at room temperature to give the intermediate 3. However, the n-butyl intermediate 3a is not detected and immediately rearranges to the product 4a, still trapped inside the capsule. Release of the intermediate and reaction with 1 in the bulk solution gives a small amount of 5a (this side product gets trapped in a capsule again).
In the case of isopropyl substitution, intermediate 3b is actually seen by NMR. It cannot rearrange to product 4b, but is released from the capsule instead and reacts with 1 to give formamide 5b. The authors explain this with the steric bulk of the isopropyl group that prevents the rearrangement inside the capsule.
As far as I know, this is the first experimental evidence for intermediates of the type of 3, which take part in the reaction mechanism suggested by Danishefsky. In addition, it also shows that the carboxylic acid – isonitrile reaction can be “catalyzed” by cavitands without the need for microwave irradiation.
