My Favorite Reaction – Azide Alkyne Huisgen Cycloaddition

The azide alkyne Huisgen cycloaddition easily qualifies as my favorite reaction and my submission to the Chemistry Carnival.  It combines simplicity with efficiency in a way that is unmatched by most other chemistries.  From clicking side chains onto polymers to conveniently synthesizing a variety of natural product analogs this click chemistry has too many uses to count.  Having performed a number of azide alkyne click reactions myself I appreciate the ease of the set up and work up.  It is almost too good to be true, though I know I don’t feel that way when I’m doing the dishes…

The reaction of azides and alkynes to form triazoles was first discovered by O. Dimroth over 100 years ago; however it was Rolf Huisgen that really capitalized on the usefulness of the reaction.  Since then it, along with other forms of click chemistry, have been promoted by K. Barry Sharpless.  Sharpless has called it the “cream of the crop” of click reactions and it is not my place to disagree with a Nobel Prize winner.

In addition to all of the wonderful characteristics of this click reaction researchers recently found a way to “unclick” using ultrasound.  Check out this Science paper if you are interested.  I’m really excited to see what applications come out of this discovery. UPDATE: Questions are now being raised about this reaction.  See this article from Bethany Halford at C&EN.

Although it may not be as well-known as other cycloadditions (thanks for stealing the show Diels-Alder…) it deserves to be recognized as a very important bit of chemistry.  If you have time please do a quick Web of Knowledge search and take a look at the applications of this amazing reaction.

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