Azides by diazotransfer

Diazotransfer from activated azides to primary amines is a fascinating process that provides a useful route to organic azides using a fairly accessible reagent – (triflyl)azide. The mechanism of the reaction remains somewhat of an enigma. There are several metals, including zinc and copper, that catalyze this process. Prof. Chi-Huey Wong has used diazotransfer chemistry in several of his elegant approaches to azasugars and put forth a mechanism that involved 5-membered intermediates. Below I am showing a representative case. You will note that protected threonine is used in this process.

Image

http://pubs.acs.org/doi/pdf/10.1021/ja0264605

The resulting azido version of threonine is a useful building block. In fact, the reason for this post is that I have been looking at ways to circumvent some of the troubles encountered in really hindered amide couplings. One way to deal with this challenge is to mask the alpha-amino group by way of an azide, which is not sterically demainding (compared to some N-protected versions). Notably, this amino acid derivative is configurationally stable (to an extent, of course). Nicolaou and co-workers have put this versatile building block to good use in their synthesis of thiostrepton (http://pubs.acs.org/doi/abs/10.1021/ja0529337).

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