Noten Efrey A, McAtee Rory C, Stephenson Corey R J
University of Michigan, Department of Chemistry, Willard Henry Dow Laboratory 930 North University Ave. Ann Arbor MI 48109 USA
Chem Sci. 2022 May 11;13(23):6942-6949. doi: 10.1039/d2sc01228f. eCollection 2022 Jun 15.
Arylethylamines are abundant motifs in myriad natural products and pharmaceuticals, so efficient methods to synthesize them are valuable in drug discovery. In this work, we disclose an intramolecular alkene aminoarylation cascade that exploits the electrophilicity of a nitrogen-centered radical to form a C-N bond, then repurposes the nitrogen atom's sulfonyl activating group as a traceless linker to form a subsequent C-C bond. This photoredox catalysis protocol enables the preparation of densely substituted arylethylamines from commercially abundant aryl sulfonamides and unactivated alkenes under mild conditions. Reaction optimization, scope, mechanism, and synthetic applications are discussed.
芳基乙胺是众多天然产物和药物中丰富的结构单元,因此高效合成它们的方法在药物发现中具有重要价值。在这项工作中,我们公开了一种分子内烯烃氨基芳基化级联反应,该反应利用以氮为中心的自由基的亲电性形成C-N键,然后将氮原子的磺酰基活化基团重新用作无痕连接基以形成后续的C-C键。这种光氧化还原催化方案能够在温和条件下从商业上丰富的芳基磺酰胺和未活化的烯烃制备高度取代的芳基乙胺。讨论了反应优化、范围、机理和合成应用。