Department of Chemistry, Princeton University, Princeton, New Jersey 08544 United States.
J Am Chem Soc. 2015 Apr 29;137(16):5300-3. doi: 10.1021/jacs.5b01983. Epub 2015 Apr 14.
We report a manganese-catalyzed aliphatic C-H azidation reaction that can efficiently convert secondary, tertiary, and benzylic C-H bonds to the corresponding azides. The method utilizes aqueous sodium azide solution as the azide source and can be performed under air. Besides its operational simplicity, the potential of this method for late-stage functionalization has been demonstrated by successful azidation of various bioactive molecules with yields up to 74%, including the important drugs pregabalin, memantine, and the antimalarial artemisinin. Azidation of celestolide with a chiral manganese salen catalyst afforded the azide product in 70% ee, representing a Mn-catalyzed enantioselective aliphatic C-H azidation reaction. Considering the versatile roles of organic azides in modern chemistry and the ubiquity of aliphatic C-H bonds in organic molecules, we envision that this Mn-azidation method will find wide application in organic synthesis, drug discovery, and chemical biology.
我们报告了一种锰催化的脂肪族 C-H 叠氮化反应，该反应能够有效地将仲、叔和苄基 C-H 键转化为相应的叠氮化物。该方法利用水合叠氮化钠溶液作为叠氮化物源，并可以在空气中进行。除了操作简单之外，该方法还具有用于后期官能化的潜力，通过成功地对各种生物活性分子进行叠氮化反应，产率高达 74%，包括重要的药物普瑞巴林、美金刚和抗疟青蒿素。用手性锰席夫碱催化剂对 celestolide 进行叠氮化反应，以 70%的 ee 值得到叠氮化物产物，代表了 Mn 催化的对映选择性脂肪族 C-H 叠氮化反应。考虑到有机叠氮化物在现代化学中的多种作用以及有机分子中脂肪族 C-H 键的普遍性，我们设想这种 Mn 叠氮化方法将在有机合成、药物发现和化学生物学中得到广泛应用。
