Remote control

Remote control of chemical reactivity ranks among the most fascinating aspects of chemistry, particularly if a network of non-covalent interactions is involved. During a recent discussion, one of my graduate students, Joanne Tan, presented an interesting paper detailing one such effect. I asked Joanne to write a summary for my blog, so here it is:

“Ever since my undergraduate years, I have always been turned off by carbohydrate chemistry. It is difficult to functionalize a carbohydrate at a specific hydroxyl group without the need for extensive protecting group manipulations. That is why I like reading about methods that allow one to perform regioselective modification of carbohydrates.

A recent JACS paper by Richard R. Schmidt and coworkers describes “the cyanide effect” – a method for the regioselective O-acylation of carbohydrates. In a typical acylation of a carbohydrate-derived diol, equatorial hydroxyl reacts preferentially. However, in the presence of cyanide anion, the axial OH is acylated instead, furnishing the kinetic product. On the basis of an NMR study, cyanide anion appears to hydrogen bond to the more acidic axial –OH, which increases its nucleophilicity. Particularly interesting is the double hydrogen bonding from the equatorial hydroxyl group to the axial oxygen atom, which serves to stabilize the resulting anion upon deprotonation by cyanide.”


6 thoughts on “Remote control

  1. The remarkacble thing is they are using DMAP in both systems (with acyl cyanide or with acyl halide/anhydride). If DMAP is a true catalyst rather than a base in both cases, one would expect a similar product distribution. Since I am pretty sure acyl halide/anhydride with DMAP provides acylpyridine, in case of the acyl cyanide the activated species must be something else.

    It would be interesting to have a look in a low-temperature NMR experiment what kind of adduct acyl cyanide forms with DMAP. Maybe there is semi-stable cyanohydrine-like tetrahedral intermediate adduct of acyl cyanide with DMAP that is the activated species.

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