EtOH-mediated cascade C(sp 3 )–H alkylation via aromatization-driven [1,6]-hydride transfer: green and divergent synthesis of spirocyclic azepino[4,3,2- cd ]indoles

The development of green and efficient methods for the construction of azepinoindole skeletons remains highly desirable yet challenging. Described herein are the EtOH-mediated cascade C(sp 3 )–H alkylation reactions of 4-dialkylamino-indole-3-carbaldehydes for green and divergent synthesis of spirocyclic azepino[4,3,2- cd ]indole derivatives. This protocol proceeded through a cascade in situ assembly of pre-aromatics/aromatization-driven [1,6]-hydride transfer/cyclization sequence, which exhibited many advantages such as green bio-sourced EtOH as the reaction medium, metal-free and redox-neutral conditions, high step-/atom-economy, water as waste, high yields, excellent diastereoselectivities (up to >20 : 1 dr), a wide substrate scope, and diverse transformations.