Research Abstract


Enhanced clickability of doubly sterically-hindered aryl azides

2011年9月5日 Scientific Reports 1 : 82 doi: 10.1038/srep00082


吉田 優1, 白石 旭2, 菅野 貴美幸2, 松下 武司3, 上本 紘平4, 植草 秀裕4 & 細谷 孝充1,2

  1. 東京医科歯科大学 大学院疾患生命科学研究部/生体材料工学研究所
  2. 東京工業大学 大学院生命理工学研究科
  3. チッソ石油化学株式会社 五井研究所
  4. 東京工業大学 大学院理工学研究科
Steric character is one of the most fundamental factors to determine the reactivity of the substrate in organic synthesis. In bimolecular reaction, the sterically-bulky group situated close to the reactive center generally prevents the approach of the reaction partner retarding the bond formation. This report describes, to the contrary, significantly enhanced reactivity of 2,6-disubstituted phenyl azides observed in catalyst-free 1,3-dipolar cycloaddition with alkynes, unexpectedly reacting faster than unsubstituted phenyl azide and even more faster than unhindered alkyl azide, despite the steric hindrance adjacent to the reactive azido group. Experimental and computational studies have indicated that the steric hindrance eliciting the inhibition of resonance between azido group and the aromatic ring is the primary cause of this apparently-paradoxical phenomenon. This is the first type of steric acceleration, indicating a possibility of designing a highly reactive functional group by strategically locating it in the sterically-congested environment.