Palamini Pierre, Schoepfer Alexandre A, Waser Jerome
Laboratory of Catalysis and Organic Synthesis, Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne, CH-1015, Lausanne, Switzerland.
Laboratory for Computational Molecular Design, Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne, CH-1015, Lausanne, Switzerland.
Angew Chem Int Ed Engl. 2025 Feb 17;64(8):e202420455. doi: 10.1002/anie.202420455. Epub 2025 Jan 2.
The azidofunctionalization of alkenes under mild conditions using commercially available starting materials and easily accessible reagents is reported based on a radical-polar crossover strategy. A broad range of alkenes, including vinyl arenes, enamides, enol ethers, vinyl sulfides, and dehydroamino esters, were regioselectively functionalized with an azide and nucleophiles such as azoles, carboxylic acids, alcohols, phosphoric acids, oximes, and phenols. The method led to a more efficient synthesis of 1,2-azidofunctionalized pharmaceutical intermediates when compared to previous approaches, resulting in both reduction of step count and increase in overall yield. The scope and limitations of these transformations were further investigated through a standard unbiased selection of 15 substrate combinations out of 1,175,658 possible using a clustering technique.
基于自由基-极性交叉策略，报道了在温和条件下使用市售起始原料和易于获得的试剂对烯烃进行叠氮官能化。包括乙烯基芳烃、烯酰胺、烯醇醚、乙烯基硫醚和脱氢氨基酯在内的多种烯烃，可通过叠氮化物和诸如唑类、羧酸、醇类、磷酸、肟类和酚类等亲核试剂进行区域选择性官能化。与先前的方法相比，该方法能更高效地合成1,2-叠氮官能化的药物中间体，减少了步骤数并提高了总产率。通过聚类技术从1,175,658种可能的组合中标准无偏选择15种底物组合，进一步研究了这些转化反应的范围和局限性。
