Diastereoselective Access to Triazolo[1,2-a]indolines via a Bio- Inspired Oxidative Cyclization of NH-Indoles

Establishing three-dimensional chemicals by using the C2-C3 Z bond of indoles has always been a research hotspot in organic synthesis; however, employing the oxidative C2-C3 Z bond of indoles to generate imine which would lead to the N1-C2 Z bond cyclization under metal-free conditions is still rare. Here, we report a bio-inspired synthesis of triazolo[1,2-a]indolines by the oxidative cyclization between NH-indoles and azomethine imines with 3,3-dimethyldioxirane as the sole oxidant under metal-free and mild conditions. This finding represents an elegant instance of tri-functionalization of NH-indoles, which provides rapid access to a broad range of triazolo[1,2-a]indolines with tetrahydroisoquinolines in one single step. Up to 86% yield and above 20:1 dr value are observed. The radical mechanism and proton migration process have been speculated.

Automated summary

In this study, a novel compound, triazolo[1,2-a]indoline, was synthesized successfully by the oxidative cyclization between NH-indoles and azomethine imines under metal-free and mild conditions. This finding provides a rapid approach for the tri-functionalization of NH-indoles.