DOI: 10.1021/acs.orglett.6c04153 ISSN: 1523-7060
Dearomative Aza-Paternò–Büchi Cycloaddition of 1 H -Indazoles for Access to Azetidine-Fused Indazolines
Xinjie Yang, Kai Hu, Chenyang Jiang, Jianjian Huang, Jianliang Li, Tengfei Pang, Zhiming Wang, Guobo Huang, Jianguo YangAbstract
Azetidine-fused N-heterocycles provide compact three-dimensional architectures of interest in medicinal chemistry, but their direct assembly from planar heteroarenes remains challenging. Here, we report a visible-light energy-transfer-catalyzed dearomative aza-Paternò–Büchi reaction of 1H-indazole-derived substrates, engaging the endocyclic imine-type unit of indazoles as an intrinsic aza component to access azetidine-fused indazoline polycycles. Mechanistic studies support preferential sensitization of the tethered styrenyl unit and reveal that protic-solvent-promoted reversible ring opening/retro aza-[2 + 2] cycloaddition accounts for the observed diastereocontrol.