A couple of weeks ago, I finished teaching the synthesis of pyridine and its derivatives in my 4th year synthesis class. Whenever I present this material, I can’t help but appreciate the value of N-oxidation. While there are N-oxides of other heterocycles (thiazole N-oxide stands out for its interesting properties), nowhere else do I feel the same level of enthusiasm about N-oxidation than in the case of pyridine. And new applications attributed to the role of N-oxides keep coming out! The one that attracted my attention comes from the lab of Nuno Maulide. This chemistry, described in a recent Angewandte paper, documents thermal modification at the 3-position of pyridine. According to the authors, the reaction likely involves a series of [2,3]-sigmatropic rearrangements. I think this “merry-go-round” sort of activation is amusing. Given the value of 3-substituted pyridines in drug discovery, this simple reaction should find many applications.
http://onlinelibrary.wiley.com/doi/10.1002/anie.201607988/abstract