Enantioselective Three-Component Radical Alkene Diazomethyl-Cyanation Enabled by Copper/Photoredox Dual Catalysis

Radical-mediated alkene dicarbofunctionalizations enable the construction of molecular complexity and the exploration of diverse C(sp3)-rich scaffolds. However, catalytic enantioselective three-component versions are underdeveloped. Herein, we report a copper/photoredox dual-catalyzed enantioselective alkene diazomethyl-cyanation. The key to the success is the selection of appropriate photocatalyst for the generation of diazomethyl radicals from α-iodonium diazo compounds and the introduction of a chiral bis(oxazoline) copper catalyst for the radical-metal crossover process. This protocol constitutes the asymmetric simultaneous incorporation of cyano and diazomethyl moieties across an alkene, providing general access to enantioenriched β-cyanodiazo compounds with tertiary or quaternary carbon stereogenic centers under mild conditions.

自由基介导的烯烃双碳官能团化反应可用于构建复杂分子骨架，并探索富含C(sp3)的多样化分子骨架。然而，催化对映选择性三组分版本的该类反应仍有待进一步开发完善。本文报道了一种铜/光氧化还原双催化的对映选择性烯烃重氮甲基氰基化反应。该反应成功的关键在于，选择合适的光催化剂以从α-碘鎓重氮化合物中生成重氮甲基自由基，同时引入手性双(恶唑啉)铜催化剂以介导自由基-金属交叉过程。本策略实现了在烯烃双键上不对称同步引入氰基与重氮甲基基团，可在温和条件下通用合成带有三级或四级碳手性中心的对映体富集型β-氰基重氮化合物。